{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:56:31Z","timestamp":1793908591262,"version":"4.8.0"},"reference-count":227,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Dis Primers"],"DOI":"10.1038\/s41572-025-00677-4","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:01:18Z","timestamp":1768464078000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Cytokine storm"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4436-9128","authenticated-orcid":false,"given":"Rajendra","family":"Karki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2421-6052","authenticated-orcid":false,"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Diorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6395-6443","authenticated-orcid":false,"given":"Thirumala-Devi","family":"Kanneganti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"677_CR1","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.it.2021.06.001","volume":"42","author":"R Karki","year":"2021","unstructured":"Karki, R. & Kanneganti, T. D. The \u2018cytokine storm\u2019: molecular mechanisms and therapeutic prospects. Trends Immunol. 42, 681\u2013705 (2021).","journal-title":"Trends Immunol."},{"key":"677_CR2","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.cell.2020.11.025","volume":"184","author":"R Karki","year":"2021","unstructured":"Karki, R. et al. Synergism of TNF-\u03b1 and IFN-\u03b3 triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell 184, 149\u2013168.e17 (2021). This article molecularly defined the mechanistic basis of cytokine storm and the positive feedback loop between inflammatory cell death (PANoptosis) and the cytokine storm.","journal-title":"Cell"},{"key":"677_CR3","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1056\/NEJMra2026131","volume":"383","author":"DC Fajgenbaum","year":"2020","unstructured":"Fajgenbaum, D. C. & June, C. H. Cytokine storm. N. Engl. J. Med. 383, 2255\u20132273 (2020). This review highlighted the key clinical and pathophysiological features of cytokine storm.","journal-title":"N. Engl. J. Med."},{"key":"677_CR4","first-page":"1216","volume":"25","author":"JL Ferrara","year":"1993","unstructured":"Ferrara, J. L., Abhyankar, S. & Gilliland, D. G. Cytokine storm of graft-versus-host disease: a critical effector role for interleukin-1. Transplant. Proc. 25, 1216\u20131217 (1993).","journal-title":"Transplant. Proc."},{"key":"677_CR5","first-page":"451","volume":"11","author":"JL Stephan","year":"1993","unstructured":"Stephan, J. L. et al. Macrophage activation syndrome and rheumatic disease in childhood: a report of four new cases. Clin. Exp. Rheumatol. 11, 451\u2013456 (1993).","journal-title":"Clin. Exp. Rheumatol."},{"key":"677_CR6","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1002\/eji.201646686","volume":"47","author":"S Ammann","year":"2017","unstructured":"Ammann, S. et al. Primary and secondary hemophagocytic lymphohistiocytosis have different patterns of T-cell activation, differentiation and repertoire. Eur. J. Immunol. 47, 364\u2013373 (2017).","journal-title":"Eur. J. Immunol."},{"key":"677_CR7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.927153","volume":"13","author":"X Zhang","year":"2022","unstructured":"Zhang, X., Zhu, L., Zhang, H., Chen, S. & Xiao, Y. CAR-T cell therapy in hematological malignancies: current opportunities and challenges. Front. Immunol. 13, 927153 (2022).","journal-title":"Front. Immunol."},{"key":"677_CR8","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.immuni.2024.03.012","volume":"57","author":"B Sundaram","year":"2024","unstructured":"Sundaram, B., Tweedell, R. E., Prasanth Kumar, S. & Kanneganti, T. D. The NLR family of innate immune and cell death sensors. Immunity 57, 674\u2013699 (2024).","journal-title":"Immunity"},{"key":"677_CR9","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.hoc.2025.02.003","volume":"39","author":"LK Meyer","year":"2025","unstructured":"Meyer, L. K., Keenan, C. & Nichols, K. E. Clinical characteristics and treatment of familial hemophagocytic lymphohistiocytosis. Hematol. Oncol. Clin. North Am. 39, 553\u2013575 (2025).","journal-title":"Hematol. Oncol. Clin. North Am."},{"key":"677_CR10","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1002\/pbc.22359","volume":"54","author":"JA Niece","year":"2010","unstructured":"Niece, J. A., Rogers, Z. R., Ahmad, N., Langevin, A. M. & McClain, K. L. Hemophagocytic lymphohistiocytosis in Texas: observations on ethnicity and race. Pediatr. Blood Cancer 54, 424\u2013428 (2010).","journal-title":"Pediatr. Blood Cancer"},{"key":"677_CR11","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/j.1651-2227.1991.tb11878.x","volume":"80","author":"JI Henter","year":"1991","unstructured":"Henter, J. I., Elinder, G., S\u00f6der, O. & Ost, A. Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis. Acta Paediatr. Scand. 80, 428\u2013435 (1991).","journal-title":"Acta Paediatr. Scand."},{"key":"677_CR12","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1136\/ard.2010.138420","volume":"70","author":"L Cuisset","year":"2011","unstructured":"Cuisset, L. et al. Mutations in the autoinflammatory cryopyrin-associated periodic syndrome gene: epidemiological study and lessons from eight years of genetic analysis in France. Ann. Rheum. Dis. 70, 495\u2013499 (2011).","journal-title":"Ann. Rheum. Dis."},{"key":"677_CR13","first-page":"105","volume":"156","author":"T Sarkisian","year":"2008","unstructured":"Sarkisian, T., Ajrapetian, H., Beglarian, A., Shahsuvarian, G. & Egiazarian, A. Familial Mediterranean fever in Armenian population. Georgian Med. News 156, 105\u2013111 (2008).","journal-title":"Georgian Med. News"},{"key":"677_CR14","first-page":"2445","volume":"25","author":"S Ozen","year":"1998","unstructured":"Ozen, S. et al. Prevalence of juvenile chronic arthritis and familial Mediterranean fever in Turkey: a field study. J. Rheumatol. 25, 2445\u20132449 (1998).","journal-title":"J. Rheumatol."},{"key":"677_CR15","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/1546-0096-8-29","volume":"8","author":"N Toplak","year":"2010","unstructured":"Toplak, N. et al. Periodic fever syndromes in Eastern and central European countries: results of a pediatric multinational survey. Pediatr. Rheumatol. Online J. 8, 29 (2010).","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"677_CR16","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1186\/s12887-021-02879-7","volume":"21","author":"D Cleves","year":"2021","unstructured":"Cleves, D. et al. Pediatric hemophagocytic lymphohistiocytosis: a rarely diagnosed entity in a developing country. BMC Pediatr. 21, 411 (2021).","journal-title":"BMC Pediatr."},{"key":"677_CR17","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000797","volume":"6","author":"J West","year":"2022","unstructured":"West, J. et al. Temporal trends in the incidence of hemophagocytic lymphohistiocytosis: a nationwide cohort study from England 2003-2018. Hemasphere 6, e797 (2022).","journal-title":"Hemasphere"},{"key":"677_CR18","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-3-031-59815-9_1","volume":"1448","author":"RQ Cron","year":"2024","unstructured":"Cron, R. Q. & Behrens, E. M. Introduction. Adv. Exp. Med. Biol. 1448, 3\u20137 (2024).","journal-title":"Adv. Exp. Med. Biol."},{"key":"677_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08940-0","author":"L Hracs","year":"2025","unstructured":"Hracs, L. et al. Global evolution of inflammatory bowel disease across epidemiologic stages. Nature https:\/\/doi.org\/10.1038\/s41586-025-08940-0 (2025).","journal-title":"Nature"},{"key":"677_CR20","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1182\/blood.2019000936","volume":"135","author":"SW Canna","year":"2020","unstructured":"Canna, S. W. & Marsh, R. A. Pediatric hemophagocytic lymphohistiocytosis. Blood 135, 1332\u20131343 (2020).","journal-title":"Blood"},{"key":"677_CR21","volume":"16","author":"A Gupta","year":"2024","unstructured":"Gupta, A., Sontakke, T., Kumar, S., Acharya, S. & Pradeep, U. Navigating the complexity: a comprehensive review of hemophagocytic lymphohistiocytosis associated with dengue infection. Cureus 16, e61128 (2024).","journal-title":"Cureus"},{"key":"677_CR22","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1111\/j.1399-3046.2008.01095.x","volume":"13","author":"JI Cohen","year":"2009","unstructured":"Cohen, J. I. Optimal treatment for chronic active Epstein-Barr virus disease. Pediatr. Transpl. 13, 393\u2013396 (2009).","journal-title":"Pediatr. Transpl."},{"key":"677_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-90766-x","volume":"15","author":"J Oppenauer","year":"2025","unstructured":"Oppenauer, J. et al. Secondary hemophagocytic lymphohistiocytosis in severe COVID-19 \u2014 a retrospective cohort study. Sci. Rep. 15, 6137 (2025).","journal-title":"Sci. Rep."},{"key":"677_CR24","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","volume":"395","author":"KE Rudd","year":"2020","unstructured":"Rudd, K. E. et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the global burden of disease study. Lancet 395, 200\u2013211 (2020). This review provides a comprehensive overview of sepsis epidemiology over a nearly 30-year period, highlighting key trends in the incidence, which has strong links to cytokine storm.","journal-title":"Lancet"},{"key":"677_CR25","first-page":"1133","volume":"34","author":"EM Behrens","year":"2007","unstructured":"Behrens, E. M., Beukelman, T., Paessler, M. & Cron, R. Q. Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J. Rheumatol. 34, 1133\u20131138 (2007).","journal-title":"J. Rheumatol."},{"key":"677_CR26","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1002\/art.39407","volume":"68","author":"AA Grom","year":"2016","unstructured":"Grom, A. A. et al. Rate and clinical presentation of macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis treated with canakinumab. Arthritis Rheumatol. 68, 218\u2013228 (2016).","journal-title":"Arthritis Rheumatol."},{"key":"677_CR27","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s40272-019-00367-1","volume":"22","author":"LA Henderson","year":"2020","unstructured":"Henderson, L. A. & Cron, R. Q. Macrophage activation syndrome and secondary hemophagocytic lymphohistiocytosis in childhood inflammatory disorders: diagnosis and management. Paediatr. Drugs 22, 29\u201344 (2020).","journal-title":"Paediatr. Drugs"},{"key":"677_CR28","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1002\/art.40417","volume":"70","author":"RE Borgia","year":"2018","unstructured":"Borgia, R. E., Gerstein, M., Levy, D. M., Silverman, E. D. & Hiraki, L. T. Features, treatment, and outcomes of macrophage activation syndrome in childhood-onset systemic lupus erythematosus. Arthritis Rheumatol. 70, 616\u2013624 (2018).","journal-title":"Arthritis Rheumatol."},{"key":"677_CR29","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1182\/blood.2023020715","volume":"143","author":"A L\u00f6fstedt","year":"2024","unstructured":"L\u00f6fstedt, A., J\u00e4dersten, M., Meeths, M. & Henter, J. I. Malignancy-associated hemophagocytic lymphohistiocytosis in Sweden: incidence, clinical characteristics, and survival. Blood 143, 233\u2013242 (2024).","journal-title":"Blood"},{"key":"677_CR30","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1080\/10428194.2024.2436037","volume":"66","author":"A Zoref-Lorenz","year":"2025","unstructured":"Zoref-Lorenz, A., Witzig, T. E., Cerhan, J. R. & Jordan, M. B. Malignancy-associated HLH: mechanisms, diagnosis, and treatment of a severe hyperinflammatory syndrome. Leuk. Lymphoma 66, 628\u2013636 (2025).","journal-title":"Leuk. Lymphoma"},{"key":"677_CR31","doi-asserted-by":"publisher","first-page":"5154","DOI":"10.1182\/blood-2013-02-485623","volume":"121","author":"DT Teachey","year":"2013","unstructured":"Teachey, D. T. et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 121, 5154\u20135157 (2013).","journal-title":"Blood"},{"key":"677_CR32","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41577-021-00547-6","volume":"22","author":"EC Morris","year":"2022","unstructured":"Morris, E. C., Neelapu, S. S., Giavridis, T. & Sadelain, M. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat. Rev. Immunol. 22, 85\u201396 (2022).","journal-title":"Nat. Rev. Immunol."},{"key":"677_CR33","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrclinonc.2017.148","volume":"15","author":"SS Neelapu","year":"2018","unstructured":"Neelapu, S. S. et al. Chimeric antigen receptor T-cell therapy \u2014 assessment and management of toxicities. Nat. Rev. Clin. Oncol. 15, 47\u201362 (2018).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"677_CR34","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1200\/JCO.20.01616","volume":"39","author":"PM Reagan","year":"2021","unstructured":"Reagan, P. M. & Neelapu, S. S. How I manage: pathophysiology and management of toxicity of chimeric antigen receptor T-cell therapies. J. Clin. Oncol. 39, 456\u2013466 (2021).","journal-title":"J. Clin. Oncol."},{"key":"677_CR35","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1056\/NEJMoa1709866","volume":"378","author":"SL Maude","year":"2018","unstructured":"Maude, S. L. et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N. Engl. J. Med. 378, 439\u2013448 (2018).","journal-title":"N. Engl. J. Med."},{"key":"677_CR36","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","volume":"377","author":"SS Neelapu","year":"2017","unstructured":"Neelapu, S. S. et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N. Engl. J. Med. 377, 2531\u20132544 (2017).","journal-title":"N. Engl. J. Med."},{"key":"677_CR37","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1056\/NEJMoa2116133","volume":"386","author":"FL Locke","year":"2022","unstructured":"Locke, F. L. et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N. Engl. J. Med. 386, 640\u2013654 (2022).","journal-title":"N. Engl. J. Med."},{"key":"677_CR38","doi-asserted-by":"publisher","first-page":"3044","DOI":"10.1200\/JCO.20.03458","volume":"39","author":"RM Myers","year":"2021","unstructured":"Myers, R. M. et al. Humanized CD19-targeted chimeric antigen receptor (CAR) T cells in CAR-naive and CAR-exposed children and young adults with relapsed or refractory acute lymphoblastic leukemia. J. Clin. Oncol. 39, 3044\u20133055 (2021).","journal-title":"J. Clin. Oncol."},{"key":"677_CR39","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1200\/JCO.20.02477","volume":"39","author":"S Kadauke","year":"2021","unstructured":"Kadauke, S. et al. Risk-adapted preemptive tocilizumab to prevent severe cytokine release syndrome after CTL019 for pediatric B-cell acute lymphoblastic leukemia: a prospective clinical trial. J. Clin. Oncol. 39, 920\u2013930 (2021).","journal-title":"J. Clin. Oncol."},{"key":"677_CR40","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1182\/blood.2019001463","volume":"134","author":"RA Gardner","year":"2019","unstructured":"Gardner, R. A. et al. Preemptive mitigation of CD19 CAR T-cell cytokine release syndrome without attenuation of antileukemic efficacy. Blood 134, 2149\u20132158 (2019).","journal-title":"Blood"},{"key":"677_CR41","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1007\/s40264-022-01194-z","volume":"45","author":"M Fusaroli","year":"2022","unstructured":"Fusaroli, M. et al. Post-marketing surveillance of CAR-T-cell therapies: analysis of the FDA adverse event reporting system (FAERS) database. Drug Saf. 45, 891\u2013908 (2022).","journal-title":"Drug Saf."},{"key":"677_CR42","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/s41435-020-0098-4","volume":"21","author":"GS Schulert","year":"2020","unstructured":"Schulert, G. S. & Cron, R. Q. The genetics of macrophage activation syndrome. Genes Immun. 21, 169\u2013181 (2020).","journal-title":"Genes Immun."},{"key":"677_CR43","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1093\/rheumatology\/kez284","volume":"59","author":"S Yasin","year":"2020","unstructured":"Yasin, S. et al. IL-18 as therapeutic target in a patient with resistant systemic juvenile idiopathic arthritis and recurrent macrophage activation syndrome. Rheumatology 59, 442\u2013445 (2020).","journal-title":"Rheumatology"},{"key":"677_CR44","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.cyto.2012.11.025","volume":"61","author":"M Shimizu","year":"2013","unstructured":"Shimizu, M., Nakagishi, Y. & Yachie, A. Distinct subsets of patients with systemic juvenile idiopathic arthritis based on their cytokine profiles. Cytokine 61, 345\u2013348 (2013).","journal-title":"Cytokine"},{"key":"677_CR45","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nri.2017.36","volume":"17","author":"T van der Poll","year":"2017","unstructured":"van der Poll, T., van de Veerdonk, F. L., Scicluna, B. P. & Netea, M. G. The immunopathology of sepsis and potential therapeutic targets. Nat. Rev. Immunol. 17, 407\u2013420 (2017).","journal-title":"Nat. Rev. Immunol."},{"key":"677_CR46","doi-asserted-by":"publisher","first-page":"257","DOI":"10.3389\/fimmu.2015.00257","volume":"6","author":"NS Merle","year":"2015","unstructured":"Merle, N. S., Noe, R., Halbwachs-Mecarelli, L., Fremeaux-Bacchi, V. & Roumenina, L. T. Complement system part II: role in immunity. Front. Immunol. 6, 257 (2015).","journal-title":"Front. Immunol."},{"key":"677_CR47","doi-asserted-by":"publisher","first-page":"6245","DOI":"10.2147\/JIR.S513367","volume":"18","author":"Q Wu","year":"2025","unstructured":"Wu, Q. et al. PANoptosis in sepsis: a central role and emerging therapeutic target. J. Inflamm. Res. 18, 6245\u20136261 (2025).","journal-title":"J. Inflamm. Res."},{"key":"677_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03767-z","volume":"20","author":"R Karki","year":"2022","unstructured":"Karki, R. & Kanneganti, T. D. Innate immunity, cytokine storm, and inflammatory cell death in COVID-19. J. Transl. Med. 20, 542 (2022).","journal-title":"J. Transl. Med."},{"key":"677_CR49","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1001\/jama.286.15.1869","volume":"286","author":"BL Warren","year":"2001","unstructured":"Warren, B. L. et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 286, 1869\u20131878 (2001).","journal-title":"JAMA"},{"key":"677_CR50","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.1001\/jama.2011.1829","volume":"306","author":"JS Boomer","year":"2011","unstructured":"Boomer, J. S. et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 306, 2594\u20132605 (2011).","journal-title":"JAMA"},{"key":"677_CR51","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1126\/science.1215173","volume":"335","author":"PJ Rauch","year":"2012","unstructured":"Rauch, P. J. et al. Innate response activator B cells protect against microbial sepsis. Science 335, 597\u2013601 (2012).","journal-title":"Science"},{"key":"677_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-016-1301-x","volume":"20","author":"R Shao","year":"2016","unstructured":"Shao, R. et al. Monocyte programmed death ligand-1 expression after 3-4 days of sepsis is associated with risk stratification and mortality in septic patients: a prospective cohort study. Crit. Care 20, 124 (2016).","journal-title":"Crit. Care"},{"key":"677_CR53","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1378\/chest.118.2.503","volume":"118","author":"CA Dinarello","year":"2000","unstructured":"Dinarello, C. A. Proinflammatory cytokines. Chest 118, 503\u2013508 (2000).","journal-title":"Chest"},{"key":"677_CR54","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.ejcb.2011.01.010","volume":"90","author":"EH Duitman","year":"2011","unstructured":"Duitman, E. H., Orinska, Z. & Bulfone-Paus, S. Mechanisms of cytokine secretion: a portfolio of distinct pathways allows flexibility in cytokine activity. Eur. J. Cell Biol. 90, 476\u2013483 (2011).","journal-title":"Eur. J. Cell Biol."},{"key":"677_CR55","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202250235","volume":"53","author":"W Chen","year":"2023","unstructured":"Chen, W., Gullett, J. M., Tweedell, R. E. & Kanneganti, T. D. Innate immune inflammatory cell death: PANoptosis and PANoptosomes in host defense and disease. Eur. J. Immunol. 53, e2250235 (2023).","journal-title":"Eur. J. Immunol."},{"key":"677_CR56","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/s41568-019-0123-y","volume":"19","author":"R Karki","year":"2019","unstructured":"Karki, R. & Kanneganti, T. D. Diverging inflammasome signals in tumorigenesis and potential targeting. Nat. Rev. Cancer 19, 197\u2013214 (2019).","journal-title":"Nat. Rev. Cancer"},{"key":"677_CR57","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.1016\/j.cell.2023.04.025","volume":"186","author":"KC Barnett","year":"2023","unstructured":"Barnett, K. C., Li, S., Liang, K. & Ting, J. P. A 360 degrees view of the inflammasome: Mechanisms of activation, cell death, and diseases. Cell 186, 2288\u20132312 (2023).","journal-title":"Cell"},{"key":"677_CR58","doi-asserted-by":"publisher","first-page":"kyac005","DOI":"10.1093\/discim\/kyac005","volume":"1","author":"TA Gleeson","year":"2022","unstructured":"Gleeson, T. A. et al. Looking into the IL-1 of the storm: are inflammasomes the link between immunothrombosis and hyperinflammation in cytokine storm syndromes? Discov. Immunol. 1, kyac005 (2022). This article covers key connections between IL-1 family cytokines and the immunopathology of cytokine storm.","journal-title":"Discov. Immunol."},{"key":"677_CR59","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1093\/rheumatology\/kez282","volume":"59","author":"S Yasin","year":"2020","unstructured":"Yasin, S. et al. IL-18 as a biomarker linking systemic juvenile idiopathic arthritis and macrophage activation syndrome. Rheumatology 59, 361\u2013366 (2020).","journal-title":"Rheumatology"},{"key":"677_CR60","doi-asserted-by":"publisher","first-page":"e329","DOI":"10.1016\/S2665-9913(22)00064-9","volume":"4","author":"J Pfeifer","year":"2022","unstructured":"Pfeifer, J. et al. Autoantibodies against interleukin-1 receptor antagonist in multisystem inflammatory syndrome in children: a multicentre retrospective cohort study. Lancet Rheumatol. 4, e329\u2013e337 (2022).","journal-title":"Lancet Rheumatol."},{"key":"677_CR61","doi-asserted-by":"publisher","first-page":"624248","DOI":"10.3389\/fped.2020.624248","volume":"8","author":"S Della Paolera","year":"2021","unstructured":"Della Paolera, S. et al. Case report: use of anakinra in multisystem inflammatory syndrome during COVID-19 pandemic. Front. Pediatr. 8, 624248 (2021).","journal-title":"Front. Pediatr."},{"key":"677_CR62","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1001\/jama.2021.9508","volume":"326","author":"R Caricchio","year":"2021","unstructured":"Caricchio, R. et al. Effect of canakinumab vs placebo on survival without invasive mechanical ventilation in patients hospitalized with severe COVID-19: a randomized clinical trial. JAMA 326, 230\u2013239 (2021).","journal-title":"JAMA"},{"key":"677_CR63","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1038\/s41591-021-01499-z","volume":"27","author":"E Kyriazopoulou","year":"2021","unstructured":"Kyriazopoulou, E. et al. Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial. Nat. Med. 27, 1752\u20131760 (2021).","journal-title":"Nat. Med."},{"key":"677_CR64","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.3390\/v15102036","volume":"15","author":"LE Jackson","year":"2023","unstructured":"Jackson, L. E. et al. Prediction of survival by IL-6 in a randomized placebo-controlled trial of anakinra in COVID-19 Cytokine storm. Viruses 15, 2036 (2023).","journal-title":"Viruses"},{"key":"677_CR65","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1084\/jem.20102538","volume":"208","author":"EE Zoller","year":"2011","unstructured":"Zoller, E. E. et al. Hemophagocytosis causes a consumptive anemia of inflammation. J. Exp. Med. 208, 1203\u20131214 (2011).","journal-title":"J. Exp. Med."},{"key":"677_CR66","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.humimm.2021.09.004","volume":"83","author":"M Ghasemzadeh","year":"2022","unstructured":"Ghasemzadeh, M., Ghasemzadeh, A. & Hosseini, E. Exhausted NK cells and cytokine storms in COVID-19: whether NK cell therapy could be a therapeutic choice. Hum. Immunol. 83, 86\u201398 (2022).","journal-title":"Hum. Immunol."},{"key":"677_CR67","doi-asserted-by":"publisher","first-page":"eadd4906","DOI":"10.1126\/sciimmunol.add4906","volume":"7","author":"P Laurent","year":"2022","unstructured":"Laurent, P. et al. Sensing of SARS-CoV-2 by pDCs and their subsequent production of IFN-I contribute to macrophage-induced cytokine storm during COVID-19. Sci. Immunol. 7, eadd4906 (2022).","journal-title":"Sci. Immunol."},{"key":"677_CR68","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1038\/nm.2053","volume":"15","author":"J Xu","year":"2009","unstructured":"Xu, J. et al. Extracellular histones are major mediators of death in sepsis. Nat. Med. 15, 1318\u20131321 (2009).","journal-title":"Nat. Med."},{"key":"677_CR69","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/nm1565","volume":"13","author":"SR Clark","year":"2007","unstructured":"Clark, S. R. et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat. Med. 13, 463\u2013469 (2007).","journal-title":"Nat. Med."},{"key":"677_CR70","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201012","volume":"217","author":"C Radermecker","year":"2020","unstructured":"Radermecker, C. et al. Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19. J. Exp. Med. 217, e20201012 (2020).","journal-title":"J. Exp. Med."},{"key":"677_CR71","volume":"5","author":"Y Zuo","year":"2020","unstructured":"Zuo, Y. et al. Neutrophil extracellular traps in COVID-19. JCI Insight 5, e138999 (2020).","journal-title":"JCI Insight"},{"key":"677_CR72","doi-asserted-by":"publisher","first-page":"73ra20","DOI":"10.1126\/scitranslmed.3001201","volume":"3","author":"GS Garcia-Romo","year":"2011","unstructured":"Garcia-Romo, G. S. et al. Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci. Transl. Med. 3, 73ra20 (2011).","journal-title":"Sci. Transl. Med."},{"key":"677_CR73","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/s41577-022-00787-0","volume":"23","author":"G Wigerblad","year":"2023","unstructured":"Wigerblad, G. & Kaplan, M. J. Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases. Nat. Rev. Immunol. 23, 274\u2013288 (2023).","journal-title":"Nat. Rev. Immunol."},{"key":"677_CR74","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1182\/blood-2013-07-514984","volume":"123","author":"KC Wildhagen","year":"2014","unstructured":"Wildhagen, K. C. et al. Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis. Blood 123, 1098\u20131101 (2014).","journal-title":"Blood"},{"key":"677_CR75","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/s41586-019-1167-6","volume":"569","author":"C Silvestre-Roig","year":"2019","unstructured":"Silvestre-Roig, C. et al. Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death. Nature 569, 236\u2013240 (2019).","journal-title":"Nature"},{"key":"677_CR76","doi-asserted-by":"publisher","first-page":"4100","DOI":"10.1182\/blood.V89.11.4100","volume":"89","author":"Y Osugi","year":"1997","unstructured":"Osugi, Y. et al. Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis. Blood 89, 4100\u20134103 (1997).","journal-title":"Blood"},{"key":"677_CR77","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/S2213-2600(20)30076-X","volume":"8","author":"Z Xu","year":"2020","unstructured":"Xu, Z. et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 8, 420\u2013422 (2020).","journal-title":"Lancet Respir. Med."},{"key":"677_CR78","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1046\/j.1365-2249.1999.00766.x","volume":"115","author":"JF Viallard","year":"1999","unstructured":"Viallard, J. F. et al. Th1 (IL-2, interferon-gamma (IFN-\u03b3)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin. Exp. Immunol. 115, 189\u2013195 (1999).","journal-title":"Clin. Exp. Immunol."},{"key":"677_CR79","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.cyto.2014.09.011","volume":"74","author":"I Raphael","year":"2015","unstructured":"Raphael, I., Nalawade, S., Eagar, T. N. & Forsthuber, T. G. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 74, 5\u201317 (2015).","journal-title":"Cytokine"},{"key":"677_CR80","doi-asserted-by":"publisher","first-page":"678","DOI":"10.3389\/fimmu.2018.00678","volume":"9","author":"ME Schmidt","year":"2018","unstructured":"Schmidt, M. E. & Varga, S. M. The CD8 T cell response to respiratory virus infections. Front. Immunol. 9, 678 (2018).","journal-title":"Front. Immunol."},{"key":"677_CR81","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2111315118","volume":"118","author":"S Galvan-Pena","year":"2021","unstructured":"Galvan-Pena, S. et al. Profound Treg perturbations correlate with COVID-19 severity. Proc. Natl Acad. Sci. USA 118, e2111315118 (2021).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"677_CR82","doi-asserted-by":"publisher","first-page":"932485","DOI":"10.3389\/fimmu.2022.932485","volume":"13","author":"KJ Bednar","year":"2022","unstructured":"Bednar, K. J., Lee, J. H. & Ort, T. Tregs in autoimmunity: insights into intrinsic brake mechanism driving pathogenesis and immune homeostasis. Front. Immunol. 13, 932485 (2022).","journal-title":"Front. Immunol."},{"key":"677_CR83","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.immuni.2006.08.010","volume":"25","author":"J Banchereau","year":"2006","unstructured":"Banchereau, J. & Pascual, V. Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity 25, 383\u2013392 (2006).","journal-title":"Immunity"},{"key":"677_CR84","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.molimm.2022.11.010","volume":"152","author":"S Thomas","year":"2022","unstructured":"Thomas, S. et al. Antibody-dependent enhancement (ADE) and the role of complement system in disease pathogenesis. Mol. Immunol. 152, 172\u2013182 (2022).","journal-title":"Mol. Immunol."},{"key":"677_CR85","doi-asserted-by":"publisher","first-page":"3207","DOI":"10.1084\/jem.20170580","volume":"214","author":"T Arkatkar","year":"2017","unstructured":"Arkatkar, T. et al. B cell-derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity. J. Exp. Med. 214, 3207\u20133217 (2017).","journal-title":"J. Exp. Med."},{"key":"677_CR86","doi-asserted-by":"publisher","first-page":"4181","DOI":"10.1128\/JVI.73.5.4181-4187.1999","volume":"73","author":"KA Staskus","year":"1999","unstructured":"Staskus, K. A. et al. Cellular tropism and viral interleukin-6 expression distinguish human herpesvirus 8 involvement in Kaposi\u2019s sarcoma, primary effusion lymphoma, and multicentric Castleman\u2019s disease. J. Virol. 73, 4181\u20134187 (1999).","journal-title":"J. Virol."},{"key":"677_CR87","doi-asserted-by":"publisher","first-page":"836","DOI":"10.7326\/0003-4819-147-12-200712180-00003","volume":"147","author":"M Bower","year":"2007","unstructured":"Bower, M. et al. Brief communication: rituximab in HIV-associated multicentric Castleman disease. Ann. Intern. Med. 147, 836\u2013839 (2007).","journal-title":"Ann. Intern. Med."},{"key":"677_CR88","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1186\/s13046-021-02148-6","volume":"40","author":"X Xiao","year":"2021","unstructured":"Xiao, X. et al. Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies. J. Exp. Clin. Cancer Res. 40, 367 (2021).","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"677_CR89","doi-asserted-by":"publisher","first-page":"dmm050762","DOI":"10.1242\/dmm.050762","volume":"17","author":"TA Gleeson","year":"2024","unstructured":"Gleeson, T. A. et al. The NLRP3 inflammasome is essential for IL-18 production in a murine model of macrophage activation syndrome. Dis. Model. Mech. 17, dmm050762 (2024).","journal-title":"Dis. Model. Mech."},{"key":"677_CR90","doi-asserted-by":"publisher","first-page":"1007705","DOI":"10.3389\/fimmu.2022.1007705","volume":"13","author":"C Moltrasio","year":"2022","unstructured":"Moltrasio, C., Romagnuolo, M. & Marzano, A. V. NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: from cryopyrin function to targeted therapies. Front. Immunol. 13, 1007705 (2022).","journal-title":"Front. Immunol."},{"key":"677_CR91","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/S2213-2600(16)00046-1","volume":"4","author":"EE Davenport","year":"2016","unstructured":"Davenport, E. E. et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir. Med. 4, 259\u2013271 (2016).","journal-title":"Lancet Respir. Med."},{"key":"677_CR92","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1038\/s12276-021-00649-0","volume":"53","author":"S Kang","year":"2021","unstructured":"Kang, S. & Kishimoto, T. Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. Exp. Mol. Med. 53, 1116\u20131123 (2021).","journal-title":"Exp. Mol. Med."},{"key":"677_CR93","doi-asserted-by":"publisher","first-page":"808799","DOI":"10.3389\/fimmu.2021.808799","volume":"12","author":"C Manosalva","year":"2021","unstructured":"Manosalva, C. et al. Role of lactate in inflammatory processes: friend or foe. Front. Immunol. 12, 808799 (2021).","journal-title":"Front. Immunol."},{"key":"677_CR94","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1002\/cbin.11545","volume":"45","author":"S Najafi","year":"2021","unstructured":"Najafi, S., Ghanavat, M., Shahrabi, S., Gatavizadeh, Z. & Saki, N. The effect of inflammatory factors and their inhibitors on the hematopoietic stem cells fate. Cell Biol. Int. 45, 900\u2013912 (2021).","journal-title":"Cell Biol. Int."},{"key":"677_CR95","doi-asserted-by":"publisher","first-page":"752","DOI":"10.4049\/jimmunol.174.2.752","volume":"174","author":"L Yang","year":"2005","unstructured":"Yang, L. et al. IFN-\u03b3 negatively modulates self-renewal of repopulating human hemopoietic stem cells. J. Immunol. 174, 752\u2013757 (2005).","journal-title":"J. Immunol."},{"key":"677_CR96","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41392-025-02178-y","volume":"10","author":"J Nie","year":"2025","unstructured":"Nie, J. et al. Deep insight into cytokine storm: from pathogenesis to treatment. Signal. Transduct. Target. Ther. 10, 112 (2025).","journal-title":"Signal. Transduct. Target. Ther."},{"key":"677_CR97","doi-asserted-by":"publisher","first-page":"237","DOI":"10.3389\/fcimb.2020.00237","volume":"10","author":"S Christgen","year":"2020","unstructured":"Christgen, S. et al. Identification of the PANoptosome: a molecular platform triggering pyroptosis, apoptosis, and necroptosis (PANoptosis). Front. Cell. Infect. Microbiol. 10, 237 (2020).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"677_CR98","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1038\/s41556-024-01491-y","volume":"26","author":"SM Man","year":"2024","unstructured":"Man, S. M. & Kanneganti, T. D. Innate immune sensing of cell death in disease and therapeutics. Nat. Cell Biol. 26, 1420\u20131433 (2024).","journal-title":"Nat. Cell Biol."},{"key":"677_CR99","doi-asserted-by":"publisher","first-page":"aag2045","DOI":"10.1126\/sciimmunol.aag2045","volume":"1","author":"T Kuriakose","year":"2016","unstructured":"Kuriakose, T. et al. ZBP1\/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Sci. Immunol. 1, aag2045 (2016).","journal-title":"Sci. Immunol."},{"key":"677_CR100","doi-asserted-by":"publisher","first-page":"102348","DOI":"10.1016\/j.coi.2023.102348","volume":"83","author":"R Karki","year":"2023","unstructured":"Karki, R. & Kanneganti, T. D. PANoptosome signaling and therapeutic implications in infection: central role for ZBP1 to activate the inflammasome and PANoptosis. Curr. Opin. Immunol. 83, 102348 (2023).","journal-title":"Curr. Opin. Immunol."},{"key":"677_CR101","doi-asserted-by":"publisher","first-page":"eabo6294","DOI":"10.1126\/sciimmunol.abo6294","volume":"7","author":"R Karki","year":"2022","unstructured":"Karki, R. et al. ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection. Sci. Immunol. 7, eabo6294 (2022). This study identified a critical link between inflammatory cell death (PANoptosis) and cytokine storm in COVID-19.","journal-title":"Sci. Immunol."},{"key":"677_CR102","doi-asserted-by":"publisher","first-page":"109858","DOI":"10.1016\/j.celrep.2021.109858","volume":"37","author":"R Karki","year":"2021","unstructured":"Karki, R. et al. ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. Cell Rep. 37, 109858 (2021).","journal-title":"Cell Rep."},{"key":"677_CR103","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/s41586-022-04896-7","volume":"607","author":"NW Hubbard","year":"2022","unstructured":"Hubbard, N. W. et al. ADAR1 mutation causes ZBP1-dependent immunopathology. Nature 607, 769\u2013775 (2022).","journal-title":"Nature"},{"key":"677_CR104","doi-asserted-by":"publisher","first-page":"2783","DOI":"10.1016\/j.cell.2023.05.005","volume":"186","author":"B Sundaram","year":"2023","unstructured":"Sundaram, B. et al. NLRP12-PANoptosome activates PANoptosis and pathology in response to heme and PAMPs. Cell 186, 2783\u20132801.e20 (2023).","journal-title":"Cell"},{"key":"677_CR105","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.05.034","author":"B Sundaram","year":"2024","unstructured":"Sundaram, B. et al. NLRC5 senses NAD+ depletion, forming a PANoptosome and driving PANoptosis and inflammation. Cell https:\/\/doi.org\/10.1016\/j.cell.2024.05.034 (2024).","journal-title":"Cell"},{"key":"677_CR106","doi-asserted-by":"publisher","first-page":"789","DOI":"10.4049\/immunohorizons.2000097","volume":"4","author":"RKS Malireddi","year":"2020","unstructured":"Malireddi, R. K. S. et al. RIPK1 distinctly regulates Yersinia-induced inflammatory cell death, PANoptosis. Immunohorizons 4, 789\u2013796 (2020).","journal-title":"Immunohorizons"},{"key":"677_CR107","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/s41586-021-03875-8","volume":"597","author":"S Lee","year":"2021","unstructured":"Lee, S. et al. AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence. Nature 597, 415\u2013419 (2021).","journal-title":"Nature"},{"key":"677_CR108","doi-asserted-by":"publisher","DOI":"10.1093\/jimmun\/vkaf042","author":"BR Sharma","year":"2025","unstructured":"Sharma, B. R., Choudhury, S. M., Abdelaal, H. M., Wang, Y. & Kanneganti, T.-D. Innate immune sensor NLRP3 drives PANoptosome formation and PANoptosis. J. Immunol. https:\/\/doi.org\/10.1093\/jimmun\/vkaf042 (2025).","journal-title":"J. Immunol."},{"key":"677_CR109","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45466-x","volume":"15","author":"JH Han","year":"2024","unstructured":"Han, J. H. et al. NINJ1 mediates inflammatory cell death, PANoptosis, and lethality during infection conditions and heat stress. Nat. Commun. 15, 1739 (2024).","journal-title":"Nat. Commun."},{"key":"677_CR110","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41586-021-03218-7","volume":"591","author":"N Kayagaki","year":"2021","unstructured":"Kayagaki, N. et al. NINJ1 mediates plasma membrane rupture during lytic cell death. Nature 591, 131\u2013136 (2021).","journal-title":"Nature"},{"key":"677_CR111","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.4049\/jimmunol.149.5.1666","volume":"149","author":"GM Doherty","year":"1992","unstructured":"Doherty, G. M. et al. Evidence for IFN-gamma as a mediator of the lethality of endotoxin and tumor necrosis factor-alpha. J. Immunol. 149, 1666\u20131670 (1992).","journal-title":"J. Immunol."},{"key":"677_CR112","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1038\/s41590-021-01035-8","volume":"22","author":"D Munnur","year":"2021","unstructured":"Munnur, D. et al. Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection. Nat. Immunol. 22, 1416\u20131427 (2021).","journal-title":"Nat. Immunol."},{"key":"677_CR113","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","volume":"25","author":"DW Lee","year":"2019","unstructured":"Lee, D. W. et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol. Blood Marrow Transplant. 25, 625\u2013638 (2019).","journal-title":"Biol. Blood Marrow Transplant."},{"key":"677_CR114","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1016\/S0140-6736(13)61048-X","volume":"383","author":"M Ramos-Casals","year":"2014","unstructured":"Ramos-Casals, M., Brito-Zer\u00f3n, P., L\u00f3pez-Guillermo, A., Khamashta, M. A. & Bosch, X. Adult haemophagocytic syndrome. Lancet 383, 1503\u20131516 (2014).","journal-title":"Lancet"},{"key":"677_CR115","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","volume":"124","author":"DW Lee","year":"2014","unstructured":"Lee, D. W. et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124, 188\u2013195 (2014).","journal-title":"Blood"},{"key":"677_CR116","doi-asserted-by":"publisher","DOI":"10.1002\/art.43052","author":"PA Nigrovic","year":"2024","unstructured":"Nigrovic, P. A. Macrophage activation syndrome. Arthritis Rheumatol. https:\/\/doi.org\/10.1002\/art.43052 (2024). This review covered the key clinical and mechanistic features of macrophage activation syndrome, which is a form of cytokine storm.","journal-title":"Arthritis Rheumatol."},{"key":"677_CR117","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1111\/cei.13057","volume":"191","author":"P Ruscitti","year":"2018","unstructured":"Ruscitti, P. et al. H-ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome. Clin. Exp. Immunol. 191, 220\u2013228 (2018).","journal-title":"Clin. Exp. Immunol."},{"key":"677_CR118","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/s10875-024-01797-4","volume":"45","author":"HA Carol","year":"2024","unstructured":"Carol, H. A. et al. Hyperferritinemia screening to aid identification and differentiation of patients with hyperinflammatory disorders. J. Clin. Immunol. 45, 4 (2024).","journal-title":"J. Clin. Immunol."},{"key":"677_CR119","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1136\/annrheumdis-2019-215211","volume":"78","author":"F Minoia","year":"2019","unstructured":"Minoia, F. et al. Development and initial validation of the MS score for diagnosis of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Ann. Rheum. Dis. 78, 1357\u20131362 (2019).","journal-title":"Ann. Rheum. Dis."},{"key":"677_CR120","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1056\/NEJMoa1215134","volume":"368","author":"SA Grupp","year":"2013","unstructured":"Grupp, S. A. et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N. Engl. J. Med. 368, 1509\u20131518 (2013).","journal-title":"N. Engl. J. Med."},{"key":"677_CR121","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1136\/annrheumdis-2015-209020","volume":"76","author":"C Bracaglia","year":"2017","unstructured":"Bracaglia, C. et al. Elevated circulating levels of interferon-\u03b3 and interferon-\u03b3-induced chemokines characterise patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Ann. Rheum. Dis. 76, 166\u2013172 (2017).","journal-title":"Ann. Rheum. Dis."},{"key":"677_CR122","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.clim.2015.06.005","volume":"160","author":"M Shimizu","year":"2015","unstructured":"Shimizu, M. et al. Interleukin-18 for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Clin. Immunol. 160, 277\u2013281 (2015).","journal-title":"Clin. Immunol."},{"key":"677_CR123","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1002\/art.42680","volume":"76","author":"KE Brodeur","year":"2024","unstructured":"Brodeur, K. E. et al. Elevation of IL-17 cytokines distinguishes Kawasaki disease from other pediatric inflammatory disorders. Arthritis Rheumatol. 76, 285\u2013292 (2024).","journal-title":"Arthritis Rheumatol."},{"key":"677_CR124","doi-asserted-by":"publisher","first-page":"3160","DOI":"10.1002\/art.38802","volume":"66","author":"F Minoia","year":"2014","unstructured":"Minoia, F. et al. Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients. Arthritis Rheumatol. 66, 3160\u20133169 (2014).","journal-title":"Arthritis Rheumatol."},{"key":"677_CR125","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27929","volume":"66","author":"MB Jordan","year":"2019","unstructured":"Jordan, M. B. et al. Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: recommendations from the North American Consortium for Histiocytosis (NACHO). Pediatr. Blood Cancer 66, e27929 (2019).","journal-title":"Pediatr. Blood Cancer"},{"key":"677_CR126","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/j.jaci.2020.09.016","volume":"146","author":"SW Canna","year":"2020","unstructured":"Canna, S. W. & Cron, R. Q. Highways to hell: mechanism-based management of cytokine storm syndromes. J. Allergy Clin. Immunol. 146, 949\u2013959 (2020).","journal-title":"J. Allergy Clin. Immunol."},{"key":"677_CR127","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-020-02989-1","volume":"24","author":"MW Adelman","year":"2020","unstructured":"Adelman, M. W. et al. The gut microbiome\u2019s role in the development, maintenance, and outcomes of sepsis. Crit. Care 24, 278 (2020).","journal-title":"Crit. Care"},{"key":"677_CR128","doi-asserted-by":"publisher","first-page":"105247","DOI":"10.1016\/j.micinf.2023.105247","volume":"26","author":"R MacCann","year":"2024","unstructured":"MacCann, R. et al. Associations between host microbiome and inflammation suggest role for host microbiome in driving COVID-19 disease severity. Microbes Infect. 26, 105247 (2024).","journal-title":"Microbes Infect."},{"key":"677_CR129","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S2468-1253(16)30119-4","volume":"2","author":"BW Haak","year":"2017","unstructured":"Haak, B. W. & Wiersinga, W. J. The role of the gut microbiota in sepsis. Lancet Gastroenterol. Hepatol. 2, 135\u2013143 (2017).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"677_CR130","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/s41586-018-0774-y","volume":"564","author":"V Staedtke","year":"2018","unstructured":"Staedtke, V. et al. Disruption of a self-amplifying catecholamine loop reduces cytokine release syndrome. Nature 564, 273\u2013277 (2018).","journal-title":"Nature"},{"key":"677_CR131","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.1172\/JCI139642","volume":"130","author":"MF Konig","year":"2020","unstructured":"Konig, M. F. et al. Preventing cytokine storm syndrome in COVID-19 using \u03b1-1 adrenergic receptor antagonists. J. Clin. Invest. 130, 3345\u20133347 (2020).","journal-title":"J. Clin. Invest."},{"key":"677_CR132","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.61700","volume":"10","author":"A Koenecke","year":"2021","unstructured":"Koenecke, A. et al. Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection. eLife 10, e61700 (2021).","journal-title":"eLife"},{"key":"677_CR133","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1136\/ard-2023-224123","volume":"82","author":"B Shakoory","year":"2023","unstructured":"Shakoory, B. et al. The 2022 EULAR\/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis\/macrophage activation syndrome (HLH\/MAS). Ann. Rheum. Dis. 82, 1271\u20131285 (2023).","journal-title":"Ann. Rheum. Dis."},{"key":"677_CR134","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1042\/cs0940557","volume":"94","author":"PJ Barnes","year":"1998","unstructured":"Barnes, P. J. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin. Sci. 94, 557\u2013572 (1998).","journal-title":"Clin. Sci."},{"key":"677_CR135","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12969-019-0309-6","volume":"17","author":"O Halyabar","year":"2019","unstructured":"Halyabar, O. et al. Calm in the midst of cytokine storm: a collaborative approach to the diagnosis and treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Pediatr. Rheumatol. Online J. 17, 7 (2019).","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"677_CR136","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1016\/j.jaip.2018.05.031","volume":"6","author":"S Ehl","year":"2018","unstructured":"Ehl, S. et al. Recommendations for the use of etoposide-based therapy and bone marrow transplantation for the treatment of HLH: consensus statements by the HLH steering committee of the histiocyte society. J. Allergy Clin. Immunol. Pract. 6, 1508\u20131517 (2018).","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"677_CR137","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1182\/blood.2018894618","volume":"133","author":"P La Ros\u00e9e","year":"2019","unstructured":"La Ros\u00e9e, P. et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood 133, 2465\u20132477 (2019).","journal-title":"Blood"},{"key":"677_CR138","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1146\/annurev-med-061813-012806","volume":"66","author":"GS Schulert","year":"2015","unstructured":"Schulert, G. S. & Grom, A. A. Pathogenesis of macrophage activation syndrome and potential for cytokine-directed therapies. Annu. Rev. Med. 66, 145\u2013159 (2015).","journal-title":"Annu. Rev. Med."},{"key":"677_CR139","doi-asserted-by":"publisher","first-page":"224ra225","DOI":"10.1126\/scitranslmed.3008226","volume":"6","author":"ML Davila","year":"2014","unstructured":"Davila, M. L. et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 6, 224ra225 (2014).","journal-title":"Sci. Transl. Med."},{"key":"677_CR140","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1056\/NEJMoa071366","volume":"358","author":"CL Sprung","year":"2008","unstructured":"Sprung, C. L. et al. Hydrocortisone therapy for patients with septic shock. N. Engl. J. Med. 358, 111\u2013124 (2008).","journal-title":"N. Engl. J. Med."},{"key":"677_CR141","first-page":"2134","volume":"54","author":"G Cavalli","year":"2015","unstructured":"Cavalli, G. & Dinarello, C. A. Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology 54, 2134\u20132144 (2015).","journal-title":"Rheumatology"},{"key":"677_CR142","doi-asserted-by":"publisher","first-page":"e358","DOI":"10.1016\/S2665-9913(20)30096-5","volume":"2","author":"P Mehta","year":"2020","unstructured":"Mehta, P., Cron, R. Q., Hartwell, J., Manson, J. J. & Tattersall, R. S. Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome. Lancet Rheumatol. 2, e358\u2013e367 (2020). This clinical review assessed the role of IL-1R antagonist treatment with anakinra in patients with different forms of cytokine storm, providing critical evidence to support the use of this therapy.","journal-title":"Lancet Rheumatol."},{"key":"677_CR143","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1097\/CCM.0000000000001402","volume":"44","author":"B Shakoory","year":"2016","unstructured":"Shakoory, B. et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase III trial. Crit. Care Med. 44, 275\u2013281 (2016).","journal-title":"Crit. Care Med."},{"key":"677_CR144","doi-asserted-by":"publisher","first-page":"100817","DOI":"10.1016\/j.xcrm.2022.100817","volume":"3","author":"K Leventogiannis","year":"2022","unstructured":"Leventogiannis, K. et al. Toward personalized immunotherapy in sepsis: the PROVIDE randomized clinical trial. Cell Rep. Med. 3, 100817 (2022).","journal-title":"Cell Rep. Med."},{"key":"677_CR145","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-067251","volume":"12","author":"A Kotsaki","year":"2022","unstructured":"Kotsaki, A. et al. ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol. BMJ Open 12, e067251 (2022).","journal-title":"BMJ Open"},{"key":"677_CR146","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","volume":"395","author":"P Mehta","year":"2020","unstructured":"Mehta, P. et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395, 1033\u20131034 (2020). This clinical correspondence piece from early on in the COVID-19 pandemic highlighted the potential life-saving effects of treating patients with COVID-19 for cytokine storm.","journal-title":"Lancet"},{"key":"677_CR147","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1002\/art.42037","volume":"74","author":"KB Onel","year":"2022","unstructured":"Onel, K. B. et al. 2021 American College of Rheumatology guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for oligoarthritis, temporomandibular joint arthritis, and systemic juvenile idiopathic arthritis. Arthritis Rheumatol. 74, 553\u2013569 (2022).","journal-title":"Arthritis Rheumatol."},{"key":"677_CR148","doi-asserted-by":"publisher","first-page":"894846","DOI":"10.3389\/fped.2022.894846","volume":"10","author":"MM Kostik","year":"2022","unstructured":"Kostik, M. M. et al. Standard and increased canakinumab dosing to quiet macrophage activation syndrome in children with systemic juvenile idiopathic arthritis. Front. Pediatr. 10, 894846 (2022).","journal-title":"Front. Pediatr."},{"key":"677_CR149","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000191","volume":"3","author":"J Garcia Borrega","year":"2019","unstructured":"Garcia Borrega, J. et al. In the eye of the storm: immune-mediated toxicities associated with CAR-T cell therapy. Hemasphere 3, e191 (2019).","journal-title":"Hemasphere"},{"key":"677_CR150","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.1016\/j.celrep.2017.11.063","volume":"21","author":"M Chmielewski","year":"2017","unstructured":"Chmielewski, M. & Abken, H. CAR T cells releasing IL-18 convert to T-Bet(high) FoxO1(low) effectors that exhibit augmented activity against advanced solid tumors. Cell Rep. 21, 3205\u20133219 (2017).","journal-title":"Cell Rep."},{"key":"677_CR151","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/clinicaltrials.gov\/study\/NCT04381936\u2009(2024)."},{"key":"677_CR152","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/clinicaltrials.gov\/study\/NCT02735707\u2009(2024)."},{"key":"677_CR153","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1001\/jama.2021.11330","volume":"326","author":"WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group.","year":"2021","unstructured":"WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: a meta-analysis. JAMA 326, 499\u2013518 (2021).","journal-title":"JAMA"},{"key":"677_CR154","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1056\/NEJMoa2100433","volume":"384","author":"REMAP-CAP Investigators","year":"2021","unstructured":"REMAP-CAP Investigators et al. Interleukin-6 receptor antagonists in critically Ill patients with covid-19. N. Engl. J. Med. 384, 1491\u20131502 (2021).","journal-title":"N. Engl. J. Med."},{"key":"677_CR155","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1016\/S0140-6736(21)00676-0","volume":"397","author":"RECOVERY Collaborative Group.","year":"2021","unstructured":"RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 397, 1637\u20131645 (2021).","journal-title":"Lancet"},{"key":"677_CR156","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/clinicaltrials.gov\/study\/NCT04320615\u2009(2021)."},{"key":"677_CR157","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/www.clinicaltrials.gov\/study\/NCT04327388\u2009(2025)."},{"key":"677_CR158","doi-asserted-by":"publisher","first-page":"110698","DOI":"10.1016\/j.biopha.2020.110698","volume":"131","author":"E Nasonov","year":"2020","unstructured":"Nasonov, E. & Samsonov, M. The role of interleukin 6 inhibitors in therapy of severe COVID-19. Biomedicine Pharmacotherapy 131, 110698 (2020).","journal-title":"Biomedicine Pharmacotherapy"},{"key":"677_CR159","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/clinicaltrials.gov\/study\/NCT04372186\u2009(2023)."},{"key":"677_CR160","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1056\/NEJMoa2030340","volume":"384","author":"C Salama","year":"2021","unstructured":"Salama, C. et al. Tocilizumab in patients hospitalized with COVID-19 pneumonia. N. Engl. J. Med. 384, 20\u201330 (2021).","journal-title":"N. Engl. J. Med."},{"key":"677_CR161","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1093\/mr\/roab119","volume":"32","author":"J Wu","year":"2022","unstructured":"Wu, J. et al. Effective therapy of tocilizumab on systemic juvenile idiopathic arthritis-associated refractory macrophage activation syndrome. Mod. Rheumatol. 32, 1114\u20131121 (2022).","journal-title":"Mod. Rheumatol."},{"key":"677_CR162","doi-asserted-by":"publisher","first-page":"712","DOI":"10.3899\/jrheum.140288","volume":"42","author":"S Yokota","year":"2015","unstructured":"Yokota, S. et al. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis under treatment with tocilizumab. J. Rheumatol. 42, 712\u2013722 (2015).","journal-title":"J. Rheumatol."},{"key":"677_CR163","doi-asserted-by":"publisher","first-page":"441","DOI":"10.3390\/cells14060441","volume":"14","author":"EP Lee","year":"2025","unstructured":"Lee, E. P. et al. Clinical value of tocilizumab in reducing mortality in refractory septic shock in children with hematologic and non-hematologic diseases. Cells 14, 441 (2025).","journal-title":"Cells"},{"key":"677_CR164","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.3390\/cancers16081512","volume":"16","author":"SH Chen","year":"2024","unstructured":"Chen, S. H. et al. Outcome of tocilizumab treatment in febrile neutropenic children with severe sepsis\/septic shock in a single-center retrospective case series. Cancers 16, 1512 (2024).","journal-title":"Cancers"},{"key":"677_CR165","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1056\/NEJMoa1911326","volume":"382","author":"F Locatelli","year":"2020","unstructured":"Locatelli, F. et al. Emapalumab in children with primary hemophagocytic lymphohistiocytosis. N. Engl. J. Med. 382, 1811\u20131822 (2020). This was the first clinical trial to show the efficacy of anti-IFN\u03b3 therapy for the treatment of pediatric patients with HLH, which led to the FDA approval of this therapy.","journal-title":"N. Engl. J. Med."},{"key":"677_CR166","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1136\/ard-2022-223739","volume":"82","author":"F De Benedetti","year":"2023","unstructured":"De Benedetti, F. et al. Efficacy and safety of emapalumab in macrophage activation syndrome. Ann. Rheum. Dis. 82, 857\u2013865 (2023).","journal-title":"Ann. Rheum. Dis."},{"key":"677_CR167","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1002\/art.42985","volume":"77","author":"S Chandrakasan","year":"2025","unstructured":"Chandrakasan, S. et al. Emapalumab treatment in patients with rheumatologic disease-associated hemophagocytic lymphohistiocytosis in the United States: a retrospective medical chart review study. Arthritis Rheumatol. 77, 226\u2013238 (2025).","journal-title":"Arthritis Rheumatol."},{"key":"677_CR168","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/apt.16717","volume":"55","author":"G Kokkotis","year":"2022","unstructured":"Kokkotis, G. et al. Systematic review with meta-analysis: COVID-19 outcomes in patients receiving anti-TNF treatments. Aliment. Pharmacol. Ther. 55, 154\u2013167 (2022).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"677_CR169","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.1097\/CCM.0b013e3182982add","volume":"41","author":"P Qiu","year":"2013","unstructured":"Qiu, P. et al. Antitumor necrosis factor therapy is associated with improved survival in clinical sepsis trials: a meta-analysis. Crit. Care Med. 41, 2419\u20132429 (2013).","journal-title":"Crit. Care Med."},{"key":"677_CR170","first-page":"2120","volume":"28","author":"S Prahalad","year":"2001","unstructured":"Prahalad, S., Bove, K. E., Dickens, D., Lovell, D. J. & Grom, A. A. Etanercept in the treatment of macrophage activation syndrome. J. Rheumatol. 28, 2120\u20132124 (2001).","journal-title":"J. Rheumatol."},{"key":"677_CR171","doi-asserted-by":"publisher","first-page":"79","DOI":"10.2147\/DHPS.S28801","volume":"5","author":"T Ali","year":"2013","unstructured":"Ali, T. et al. Clinical use of anti-TNF therapy and increased risk of infections. Drug Healthc. Patient Saf. 5, 79\u201399 (2013).","journal-title":"Drug Healthc. Patient Saf."},{"key":"677_CR172","doi-asserted-by":"publisher","first-page":"3493","DOI":"10.1182\/blood.2021014860","volume":"139","author":"Q Zhang","year":"2022","unstructured":"Zhang, Q. et al. A study of ruxolitinib response-based stratified treatment for pediatric hemophagocytic lymphohistiocytosis. Blood 139, 3493\u20133504 (2022).","journal-title":"Blood"},{"key":"677_CR173","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2031994","author":"AC Kalil","year":"2020","unstructured":"Kalil, A. C. et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N. Engl. J. Med. https:\/\/doi.org\/10.1056\/nejmoa2031994 (2020). This was the first clinical trial to show that the JAK inhibitor baricitinib had efficacy in patients with COVID-19, which was a key step towards the FDA approval of this therapy.","journal-title":"N. Engl. J. Med."},{"key":"677_CR174","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/978-3-031-59815-9_35","volume":"1448","author":"JI Henter","year":"2024","unstructured":"Henter, J. I. & von Bahr Greenwood, T. Etoposide therapy of cytokine storm syndromes. Adv. Exp. Med. Biol. 1448, 525\u2013551 (2024).","journal-title":"Adv. Exp. Med. Biol."},{"key":"677_CR175","doi-asserted-by":"publisher","first-page":"84","DOI":"10.4049\/jimmunol.1302282","volume":"192","author":"TS Johnson","year":"2014","unstructured":"Johnson, T. S. et al. Etoposide selectively ablates activated T cells to control the immunoregulatory disorder hemophagocytic lymphohistiocytosis. J. Immunol. 192, 84\u201391 (2014).","journal-title":"J. Immunol."},{"key":"677_CR176","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1002\/jha2.57","volume":"1","author":"MC Nicholson","year":"2020","unstructured":"Nicholson, M. C. et al. Etoposide-based treatment of adult HLH is associated with high biochemical response but poor survival outcomes. EJHaem 1, 277\u2013280 (2020).","journal-title":"EJHaem"},{"key":"677_CR177","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2021-001906","volume":"7","author":"MT Janssen","year":"2021","unstructured":"Janssen, M. T., Ramiro, S., Mostard, R. L., Magro-Checa, C. & Landewe, R. B. Three-month and six-month outcomes of patients with COVID-19 associated hyperinflammation treated with short-term immunosuppressive therapy: follow-up of the CHIC study. RMD Open 7, e001906 (2021).","journal-title":"RMD Open"},{"key":"677_CR178","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.31431","volume":"72","author":"X Li","year":"2025","unstructured":"Li, X. et al. Health-related quality of life among discharged patients with hemophagocytic lymphohistiocytosis: a follow-up study. Pediatr. Blood Cancer 72, e31431 (2025).","journal-title":"Pediatr. Blood Cancer"},{"key":"677_CR179","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/s41591-018-0036-4","volume":"24","author":"M Norelli","year":"2018","unstructured":"Norelli, M. et al. Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nat. Med. 24, 739\u2013748 (2018). This study elucidated the molecular role of monocytes in producing both IL-1 and IL-6 in CAR T cell-induced cytokine storm, known as cytokine release syndrome.","journal-title":"Nat. Med."},{"key":"677_CR180","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.4049\/jimmunol.2200808","volume":"210","author":"PY Lee","year":"2023","unstructured":"Lee, P. Y. & Cron, R. Q. The multifaceted immunology of cytokine storm syndrome. J. Immunol. 210, 1015\u20131024 (2023).","journal-title":"J. Immunol."},{"key":"677_CR181","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1097\/00003246-199707000-00010","volume":"25","author":"SM Opal","year":"1997","unstructured":"Opal, S. M. et al. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group. Crit. Care Med. 25, 1115\u20131124 (1997).","journal-title":"Crit. Care Med."},{"key":"677_CR182","doi-asserted-by":"publisher","first-page":"e393","DOI":"10.1016\/S2665-9913(20)30164-8","volume":"2","author":"T Huet","year":"2020","unstructured":"Huet, T. et al. Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol. 2, e393\u2013e400 (2020).","journal-title":"Lancet Rheumatol."},{"key":"677_CR183","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/www.clinicaltrials.gov\/study\/NCT04443881 (2021)."},{"key":"677_CR184","doi-asserted-by":"publisher","first-page":"3123","DOI":"10.1182\/bloodadvances.2020002328","volume":"4","author":"P Strati","year":"2020","unstructured":"Strati, P. et al. Clinical efficacy of anakinra to mitigate CAR T-cell therapy-associated toxicity in large B-cell lymphoma. Blood Adv. 4, 3123\u20133127 (2020).","journal-title":"Blood Adv."},{"key":"677_CR185","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s13075-025-03493-z","volume":"27","author":"H de Boysson","year":"2025","unstructured":"de Boysson, H. et al. Four months of treatment with anakinra combined with glucocorticoids for giant cell arteritis: a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Res. Ther. 27, 122 (2025).","journal-title":"Arthritis Res. Ther."},{"key":"677_CR186","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1002\/art.33412","volume":"64","author":"HR Schumacher Jr.","year":"2012","unstructured":"Schumacher, H. R. Jr. et al. Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a phase II randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 64, 876\u2013884 (2012).","journal-title":"Arthritis Rheum."},{"key":"677_CR187","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1111\/ijcp.12521","volume":"68","author":"JD Hirsch","year":"2014","unstructured":"Hirsch, J. D., Gnanasakthy, A., Lale, R., Choi, K. & Sarkin, A. J. Efficacy of canakinumab vs. triamcinolone acetonide according to multiple gouty arthritis-related health outcomes measures. Int. J. Clin. Pract. 68, 1503\u20131507 (2014).","journal-title":"Int. J. Clin. Pract."},{"key":"677_CR188","doi-asserted-by":"publisher","first-page":"P68","DOI":"10.1186\/ar1589","volume":"7","author":"A Gibbs","year":"2005","unstructured":"Gibbs, A. et al. Anakinra (Kineret) in psoriasis and psoriatic arthritis: a single-center, open-label, pilot study. Arthritis Res. Ther. 7, P68 (2005).","journal-title":"Arthritis Res. Ther."},{"key":"677_CR189","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1093\/rheumatology\/keae440","volume":"64","author":"R Caorsi","year":"2025","unstructured":"Caorsi, R. et al. Long-term efficacy of MAS825, a bispecific anti-IL1\u03b2 and IL-18 monoclonal antibody, in two patients with systemic JIA and recurrent episodes of macrophage activation syndrome. Rheumatology 64, 1528\u20131533 (2025).","journal-title":"Rheumatology"},{"key":"677_CR190","first-page":"A139","volume":"6","author":"S Hasni","year":"2019","unstructured":"Hasni, S. et al. 183 A phase 1B\/2A trial of tofacitinib, an oral Janus kinase inhibitor, in systemic lupus erythematosus. Lupus Sci. Med. 6, A139 (2019).","journal-title":"Lupus Sci. Med."},{"key":"677_CR191","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1016\/j.bbmt.2012.03.013","volume":"18","author":"SW Choi","year":"2012","unstructured":"Choi, S. W. et al. TNF-inhibition with etanercept for graft-versus-host disease prevention in high-risk HCT: lower TNFR1 levels correlate with better outcomes. Biol. Blood Marrow Transpl. 18, 1525\u20131532 (2012).","journal-title":"Biol. Blood Marrow Transpl."},{"key":"677_CR192","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1016\/j.bbmt.2014.05.023","volume":"20","author":"E Gatza","year":"2015","unstructured":"Gatza, E. et al. Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol. Blood Marrow Transpl. 20, 1426\u20131434 (2015).","journal-title":"Biol. Blood Marrow Transpl."},{"key":"677_CR193","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s00281-017-0639-8","volume":"39","author":"BG Chousterman","year":"2017","unstructured":"Chousterman, B. G., Swirski, F. K. & Weber, G. F. Cytokine storm and sepsis disease pathogenesis. Semin. Immunopathology 39, 517\u2013528 (2017).","journal-title":"Semin. Immunopathology"},{"key":"677_CR194","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.1097\/CCM.0b013e3182982add","volume":"41","author":"P Qiu","year":"2013","unstructured":"Qiu, P. et al. Antitumor necrosis factor therapy is associated with improved survival in clinical sepsis trials. Crit. Care Med. 41, 2419\u20132429 (2013).","journal-title":"Crit. Care Med."},{"key":"677_CR195","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1053\/j.gastro.2020.04.043","volume":"159","author":"I Rodriguez-Lago","year":"2020","unstructured":"Rodriguez-Lago, I. et al. Characteristics and prognosis of patients with inflammatory bowel disease during the SARS-CoV-2 pandemic in the Basque Country (Spain). Gastroenterology 159, 781\u2013783 (2020).","journal-title":"Gastroenterology"},{"key":"677_CR196","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1111\/apt.15897","volume":"52","author":"CH Waggershauser","year":"2020","unstructured":"Waggershauser, C. H. et al. Letter: immunotherapy in IBD patients in a SARS-CoV-2 endemic area. Aliment. Pharmacol. Ther. 52, 898\u2013899 (2020).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"677_CR197","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1001\/jama.2023.11043","volume":"330","author":"JA O\u2019Halloran","year":"2023","unstructured":"O\u2019Halloran, J. A. et al. Abatacept, cenicriviroc, or infliximab for treatment of adults hospitalized with covid-19 pneumonia: a randomized clinical trial. JAMA 330, 328\u2013339 (2023).","journal-title":"JAMA"},{"key":"677_CR198","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/clinicaltrials.gov\/study\/NCT04324021 (2022)."},{"key":"677_CR199","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1053\/j.gastro.2004.05.011","volume":"127","author":"D Hommes","year":"2004","unstructured":"Hommes, D. et al. Fontolizumab (Huzaf), a humanized anti-IFN-gamma antibody, has clinical activity and excellent tolerability in moderate to severe Crohn\u2019s disease. Gastroenterology 127, 332 (2004).","journal-title":"Gastroenterology"},{"key":"677_CR200","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1182\/blood-2024-203214","volume":"144","author":"Z Wang","year":"2024","unstructured":"Wang, Z. et al. Rovadicitinib in patients with hemophagocytic lymphohistiocytosis: a single arm, open-label, phase I study. Blood 144, 806 (2024).","journal-title":"Blood"},{"key":"677_CR201","doi-asserted-by":"publisher","first-page":"S746","DOI":"10.1093\/ecco-jcc\/jjz186","volume":"14","author":"G Rogler","year":"2020","unstructured":"Rogler, G. Efficacy of JAK inhibitors in Crohn\u2019s disease. J. Crohns Colitis 14, S746\u2013S754 (2020).","journal-title":"J. Crohns Colitis"},{"key":"677_CR202","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.jaad.2017.01.053","volume":"77","author":"JF Merola","year":"2017","unstructured":"Merola, J. F. et al. Efficacy of tofacitinib for the treatment of nail psoriasis: two 52-week, randomized, controlled phase 3 studies in patients with moderate-to-severe plaque psoriasis. J. Am. Acad. Dermatol. 77, 79\u201387.e1 (2017).","journal-title":"J. Am. Acad. Dermatol."},{"key":"677_CR203","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1111\/bjd.14018","volume":"173","author":"KA Papp","year":"2015","unstructured":"Papp, K. A. et al. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials. Br. J. Dermatology 173, 949\u2013961 (2015).","journal-title":"Br. J. Dermatology"},{"key":"677_CR204","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1136\/ard.2010.134254","volume":"70","author":"P Quartier","year":"2011","unstructured":"Quartier, P. et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS) trial. Ann. Rheum. Dis. 70, 747\u2013754 (2011).","journal-title":"Ann. Rheum. Dis."},{"key":"677_CR205","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.3899\/jrheum.111549","volume":"39","author":"D Nordstr\u00f6m","year":"2012","unstructured":"Nordstr\u00f6m, D. et al. Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset Still\u2019s disease. An open, randomized, multicenter study. J. Rheumatol. 39, 2008\u20132011 (2012).","journal-title":"J. Rheumatol."},{"key":"677_CR206","doi-asserted-by":"publisher","first-page":"2196","DOI":"10.1002\/1529-0131(199812)41:12<2196::AID-ART15>3.0.CO;2-2","volume":"41","author":"B Bresnihan","year":"1998","unstructured":"Bresnihan, B. et al. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum. 41, 2196\u20132204 (1998).","journal-title":"Arthritis Rheum."},{"key":"677_CR207","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1056\/NEJMoa055137","volume":"355","author":"R Goldbach-Mansky","year":"2006","unstructured":"Goldbach-Mansky, R. et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1\u03b2 inhibition. N. Engl. J. Med. 355, 581\u2013592 (2006).","journal-title":"N. Engl. J. Med."},{"key":"677_CR208","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.1056\/NEJM200306193482523","volume":"348","author":"PN Hawkins","year":"2003","unstructured":"Hawkins, P. N., Lachmann, H. J. & McDermott, M. F. Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N. Engl. J. Med. 348, 2583\u20132584 (2003). This study, along with other clinical trials in the early 2000s, laid the foundation for the clinical use of anti-IL-1 blockade as a treatment strategy in cytokine storm associated with mutations driving aberrant inflammasome activation.","journal-title":"N. Engl. J. Med."},{"key":"677_CR209","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.1056\/NEJMoa1706314","volume":"378","author":"F De Benedetti","year":"2018","unstructured":"De Benedetti, F. et al. Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. N. Engl. J. Med. 378, 1908\u20131919 (2018).","journal-title":"N. Engl. J. Med."},{"key":"677_CR210","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/S0140-6736(08)60454-7","volume":"371","author":"S Yokota","year":"2008","unstructured":"Yokota, S. et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet 371, 998\u20131006 (2008).","journal-title":"Lancet"},{"key":"677_CR211","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1158\/1078-0432.CCR-14-1678","volume":"21","author":"A Deisseroth","year":"2015","unstructured":"Deisseroth, A. et al. FDA approval: siltuximab for the treatment of patients with multicentric castleman disease. Clin. Cancer Res. 21, 950\u2013954 (2015).","journal-title":"Clin. Cancer Res."},{"key":"677_CR212","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1634\/theoncologist.2018-0028","volume":"23","author":"RQ Le","year":"2018","unstructured":"Le, R. Q. et al. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. Oncologist 23, 943\u2013947 (2018).","journal-title":"Oncologist"},{"key":"677_CR213","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/S0140-6736(08)60453-5","volume":"371","author":"JS Smolen","year":"2008","unstructured":"Smolen, J. S. et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 371, 987\u2013997 (2008).","journal-title":"Lancet"},{"key":"677_CR214","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1056\/NEJMoa1613849","volume":"377","author":"JH Stone","year":"2017","unstructured":"Stone, J. H. et al. Trial of tocilizumab in giant-cell arteritis. N. Engl. J. Med. 377, 317\u2013328 (2017).","journal-title":"N. Engl. J. Med."},{"key":"677_CR215","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1056\/NEJMoa2028700","volume":"384","author":"IO Rosas","year":"2021","unstructured":"Rosas, I. O. et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N. Engl. J. Med. 384, 1503\u20131516 (2021).","journal-title":"N. Engl. J. Med."},{"key":"677_CR216","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1016\/S0140-6736(99)05246-0","volume":"354","author":"R Maini","year":"1999","unstructured":"Maini, R. et al. Infliximab (chimeric anti-tumour necrosis factor \u03b1 monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 354, 1932\u20131939 (1999).","journal-title":"Lancet"},{"key":"677_CR217","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/0140-6736(93)91375-V","volume":"342","author":"B Derkx","year":"1993","unstructured":"Derkx, B. et al. Tumour-necrosis-factor antibody treatment in Crohn\u2019s disease. Lancet 342, 173\u2013174 (1993).","journal-title":"Lancet"},{"key":"677_CR218","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1056\/NEJM199710093371502","volume":"337","author":"SR Targan","year":"1997","unstructured":"Targan, S. R. et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor \u03b1 for Crohn\u2019s disease. Crohn\u2019s Disease cA2 Study Group. N. Engl. J. Med. 337, 1029\u20131035 (1997).","journal-title":"N. Engl. J. Med."},{"key":"677_CR219","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.1056\/NEJMoa050516","volume":"353","author":"P Rutgeerts","year":"2005","unstructured":"Rutgeerts, P. et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 353, 2462\u20132476 (2005).","journal-title":"N. Engl. J. Med."},{"key":"677_CR220","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1111\/j.1365-2133.2005.06688.x","volume":"152","author":"KA Papp","year":"2005","unstructured":"Papp, K. A. et al. A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br. J. Dermatology 152, 1304\u20131312 (2005).","journal-title":"Br. J. Dermatology"},{"key":"677_CR221","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1056\/NEJMoa050580","volume":"354","author":"MA Berry","year":"2006","unstructured":"Berry, M. A. et al. Evidence of a role of tumor necrosis factor \u03b1 in refractory asthma. N. Engl. J. Med. 354, 697\u2013708 (2006).","journal-title":"N. Engl. J. Med."},{"key":"677_CR222","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1182\/bloodadvances.2018025858","volume":"3","author":"DT Lounder","year":"2019","unstructured":"Lounder, D. T., Bin, Q., de Min, C. & Jordan, M. B. Treatment of refractory hemophagocytic lymphohistiocytosis with emapalumab despite severe concurrent infections. Blood Adv. 3, 47\u201350 (2019).","journal-title":"Blood Adv."},{"key":"677_CR223","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.jinf.2020.04.017","volume":"81","author":"F Cantini","year":"2020","unstructured":"Cantini, F. et al. Baricitinib therapy in COVID-19: a pilot study on safety and clinical impact. J. Infect. 81, 318\u2013356 (2020).","journal-title":"J. Infect."},{"key":"677_CR224","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1016\/S0140-6736(21)01255-1","volume":"398","author":"N Ruperto","year":"2021","unstructured":"Ruperto, N. et al. Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial. Lancet 398, 1984\u20131996 (2021).","journal-title":"Lancet"},{"key":"677_CR225","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1182\/blood.2020004823","volume":"135","author":"M Jagasia","year":"2020","unstructured":"Jagasia, M. et al. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood 135, 1739\u20131749 (2020).","journal-title":"Blood"},{"key":"677_CR226","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1056\/NEJMoa1109071","volume":"367","author":"R Fleischmann","year":"2012","unstructured":"Fleischmann, R. et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N. Engl. J. Med. 367, 495\u2013507 (2012).","journal-title":"N. Engl. J. Med."},{"key":"677_CR227","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1056\/NEJMoa1606910","volume":"376","author":"WJ Sandborn","year":"2017","unstructured":"Sandborn, W. J. et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 376, 1723\u20131736 (2017).","journal-title":"N. Engl. J. Med."}],"container-title":["Nature Reviews Disease Primers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41572-025-00677-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41572-025-00677-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41572-025-00677-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:01:35Z","timestamp":1768464095000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41572-025-00677-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,15]]},"references-count":227,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["677"],"URL":"https:\/\/doi.org\/10.1038\/s41572-025-00677-4","relation":{},"ISSN":["2056-676X"],"issn-type":[{"value":"2056-676X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,15]]},"assertion":[{"value":"5 December 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2026","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1"}}