{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T07:13:11Z","timestamp":1789197191606,"version":"build-2803163510"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100015269","name":"Magyarorsz\u00e1g Korm\u00e1nya","doi-asserted-by":"publisher","award":["\u00daNKP-21-2-I-PTE-1230"],"award-info":[{"award-number":["\u00daNKP-21-2-I-PTE-1230"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Magyarorsz\u00e1g Korm\u00e1nya","doi-asserted-by":"publisher","award":["\u00daNKP-22-3-I-PTE-1492"],"award-info":[{"award-number":["\u00daNKP-22-3-I-PTE-1492"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Magyarorsz\u00e1g Korm\u00e1nya","doi-asserted-by":"publisher","award":["EK\u00d6P-24-3-II-PTE-168"],"award-info":[{"award-number":["EK\u00d6P-24-3-II-PTE-168"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Magyarorsz\u00e1g Korm\u00e1nya","doi-asserted-by":"publisher","award":["EK\u00d6P-24-3-II-PTE-117"],"award-info":[{"award-number":["EK\u00d6P-24-3-II-PTE-117"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009594","name":"University of P\u00e9cs","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009594","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Multiple myeloma (MM) is an inflammation-driven plasma cell malignancy influenced by the bone marrow microenvironment. Dysregulated cytokine networks and neuroimmune factors may contribute to disease progression and extramedullary disease (EMD), a high-risk variant with poor prognosis.\u00a0Plasma levels of 13 cytokines (IFN-\u03b3, IL-1\u03b2, IL-2, IL-3, IL-6, IL-8, IL-9, IL-10, IL-17A, MCP-1, MIP-1\u03b1, TGF-\u03b1, TNF-\u03b1) and PACAP-38 \u2013 wich is an antiinflammatory neuropeptide-were measured in 48 MM patients and 10 healthy controls using ELISA and Luminex assays.\u00a0MM patients exhibited elevated IFN-\u03b3, IL-10, MCP-1 and reduced IL-17A, TGF-\u03b1 compared to controls. Active disease correlated with higher IL-10 and TNF-\u03b1, while EMD showed marked increases in IFN-\u03b3, IL-10, MCP-1, PACAP-38 and decreased TGF-\u03b1. IL-6, IL-10, IL-9, IL-17A, and TGF-\u03b1 were associated with progression-free survival. PACAP-38 correlated positively with IL-10 and negatively with MCP-1 and MIP-1\u03b1\n                    <jats:bold>.\u00a0<\/jats:bold>\n                    MM and EMD are characterized by distinct inflammatory and neuropeptide profiles with prognostic relevance. Integrating these biomarkers into risk models may improve stratification and guide personalized therapy. Larger studies are needed to validate clinical utility.\n                  <\/jats:p>","DOI":"10.1007\/s11357-026-02494-3","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:56:04Z","timestamp":1789196164000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The relationship between inflammation and multiple myeloma: insights into alterations and prognostic value"],"prefix":"10.1007","author":[{"given":"T\u00fcnde","family":"T\u00f3th","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussain","family":"Alizadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Be\u00e1ta","family":"Polg\u00e1r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e1ta","family":"Csal\u00f3di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1gnes","family":"Kem\u00e9ny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f3ra","family":"Regl\u0151di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Faludi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borb\u00e1la","family":"Peth\u0151","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Tam\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"2494_CR1","first-page":"7","volume":"69","author":"RL Siegel","year":"2019","unstructured":"Siegel RL. Miller KD et Jemal A. Cancer statistics, CA Cancer J Clin. 2019;69:7\u201334.","journal-title":"Cancer statistics, CA Cancer J Clin"},{"key":"2494_CR2","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nrc.2017.63","volume":"17","author":"C Pawlyn","year":"2017","unstructured":"Pawlyn C, Morgan GJ. Evolutionary biology of high-risk multiple myeloma. Nat Rev Cancer. 2017;17:543\u201356.","journal-title":"Nat Rev Cancer"},{"issue":"4","key":"2494_CR3","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.celrep.2015.06.059","volume":"12","author":"AM Roccaro","year":"2015","unstructured":"Roccaro AM, et al. CXCR4 regulates extra-medullary myeloma through epithelial-mesenchymal-transition-like transcriptional activation. Cell Rep. 2015;12(4):622\u201335. https:\/\/doi.org\/10.1016\/j.celrep.2015.06.059.","journal-title":"Cell Rep"},{"key":"2494_CR4","doi-asserted-by":"publisher","first-page":"9710","DOI":"10.3390\/curroncol30110705","volume":"30","author":"M Fazio","year":"2023","unstructured":"Fazio M, Del Fabro V, Parrinello NL, et al. Multiple myeloma in 2023 ways: from trials to real life. Curr Oncol. 2023;30:9710\u201333.","journal-title":"Curr Oncol"},{"key":"2494_CR5","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyad306","author":"A Rafae","year":"2023","unstructured":"Rafae A, van Rhee F, Al Hadidi S. Perspectives on the treatment of multiple myeloma. Oncologist. 2023. https:\/\/doi.org\/10.1093\/oncolo\/oyad306.","journal-title":"Oncologist"},{"key":"2494_CR6","first-page":"1","volume":"42","author":"MV Mateos","year":"2022","unstructured":"Mateos MV, Nooka AK, Larson SM. Moving Toward a Cure for Myeloma. Am Soc Clin Oncol Educ Book. 2022;42:1\u201312.","journal-title":"Am Soc Clin Oncol Educ Book"},{"issue":"11","key":"2494_CR7","doi-asserted-by":"publisher","first-page":"8975","DOI":"10.3390\/curroncol29110705","volume":"29","author":"M Ho","year":"2022","unstructured":"Ho M, Xiao A, Yi D, Zanwar S, Bianchi G. Treating multiple myeloma in the context of the bone marrow microenvironment. Curr Oncol. 2022;29(11):8975\u20139005. https:\/\/doi.org\/10.3390\/curroncol29110705.","journal-title":"Curr Oncol"},{"key":"2494_CR8","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/s41590-021-00931-3","volume":"22","author":"MME de Jong","year":"2021","unstructured":"de Jong MME, Kellermayer Z, Papazian N, et al. The multiple myeloma microenvironment is defined by an inflammatory stromal cell landscape. Nat Immunol. 2021;22:769\u201380.","journal-title":"Nat Immunol"},{"issue":"11","key":"2494_CR9","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1631\/jzus.B2200277","volume":"23","author":"X Yue","year":"2022","unstructured":"Yue X, et al. High levels of serum IL-10 indicate disease progression, extramedullary involvement, and poor prognosis in multiple myeloma. J Zhejiang Univ Sci B. 2022;23(11):968\u201374. https:\/\/doi.org\/10.1631\/jzus.B2200277.","journal-title":"J Zhejiang Univ Sci B"},{"key":"2494_CR10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1169071","volume":"14","author":"Y Liu","year":"2023","unstructured":"Liu Y, et al. A combination of pre-infusion serum ferritin, CRP and IL-6 predicts outcome in relapsed\/refractory multiple myeloma patients treated with CAR-T cells. Front Immunol. 2023;14:1169071. https:\/\/doi.org\/10.3389\/fimmu.2023.1169071.","journal-title":"Front Immunol"},{"issue":"5-6","key":"2494_CR11","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1007\/s10787-006-1532-6","volume":"14","author":"RE Kast","year":"2006","unstructured":"Kast RE. Aspirin, TNF-alpha, NFkB, and survival in multiple myeloma: the importance of measuring TNF-alpha. Inflammopharmacology. 2006;14(5\u20136):256\u20139. https:\/\/doi.org\/10.1007\/s10787-006-1532-6.","journal-title":"Inflammopharmacology"},{"issue":"13","key":"2494_CR12","doi-asserted-by":"publisher","first-page":"10801","DOI":"10.3390\/ijms241310801","volume":"24","author":"T T\u00f3th","year":"2023","unstructured":"T\u00f3th T, Alizadeh H, Polg\u00e1r B, Csal\u00f3di R, Regl\u0151di D, Tam\u00e1s A. Diagnostic and Prognostic Value of PACAP in Multiple Myeloma. Int J Mol Sci. 2023;24(13):10801. https:\/\/doi.org\/10.3390\/ijms241310801.","journal-title":"Int J Mol Sci"},{"issue":"6","key":"2494_CR13","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1007\/s12185-022-03364-2","volume":"115","author":"DL Murray","year":"2022","unstructured":"Murray DL. Bringing mass spectrometry into the care of patients with multiple myeloma. Int J Hematol. 2022;115(6):790\u20138. https:\/\/doi.org\/10.1007\/s12185-022-03364-2","journal-title":"Int J Hematol"},{"issue":"4","key":"2494_CR14","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.clml.2023.01.005","volume":"23","author":"J Hillengass","year":"2023","unstructured":"Hillengass J, Martin T, Puig N, Paiva B, Usmani S, Kumar S, et al. Disease Monitoring In Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2023;23(4):244\u20138. https:\/\/doi.org\/10.1016\/j.clml.2023.01.005","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"2494_CR15","doi-asserted-by":"publisher","first-page":"21","DOI":"10.4065\/78.1.21","volume":"78","author":"RA Kyle","year":"2003","unstructured":"Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78:21\u201333. https:\/\/doi.org\/10.4065\/78.1.21.","journal-title":"Mayo Clin Proc"},{"key":"2494_CR16","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/ejh.12478","volume":"95","author":"SS Chawla","year":"2015","unstructured":"Chawla SS, Kumar SK, Dispenzieri A, Greenberg AJ, Larson DR, Kyle RA, et al. Clinical course and prognosis of non-secretory multiple myeloma. Eur J Haematol. 2015;95:57\u201364. https:\/\/doi.org\/10.1111\/ejh.12478.","journal-title":"Eur J Haematol"},{"key":"2494_CR17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147470","volume":"22","author":"AM Soliman","year":"2021","unstructured":"Soliman AM, Das S, Teoh SL. Next-generation biomarkers in multiple myeloma: understanding the molecular basis for potential use in diagnosis and prognosis. Int J Mol Sci. 2021;22:7470. https:\/\/doi.org\/10.3390\/ijms22147470.","journal-title":"Int J Mol Sci"},{"key":"2494_CR18","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.trsl.2018.05.003","volume":"201","author":"A Levin","year":"2018","unstructured":"Levin A, Hari P, Dhakal B. Novel biomarkers in multiple myeloma. Transl Res. 2018;201:49\u201359. https:\/\/doi.org\/10.1016\/j.trsl.2018.05.003.","journal-title":"Transl Res"},{"key":"2494_CR19","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.3892\/or.2019.7261","volume":"42","author":"J Hou","year":"2019","unstructured":"Hou J, Wei R, Qian J, Wang R, Fan Z, Gu C, et al. The impact of the bone marrow microenvironment on multiple myeloma (Review) Oncol. Rep. 2019;42:1272\u201382. https:\/\/doi.org\/10.3892\/or.2019.7261.","journal-title":"Rep"},{"key":"2494_CR20","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1038\/leu.2017.102","volume":"31","author":"SV Glavey","year":"2017","unstructured":"Glavey SV, Naba A, Manier S, Clauser K, Tahri S, Park J, et al. Proteomic characterization of human multiple myeloma bone marrow extracellular matrix. Leukemia. 2017;31:2426\u201334. https:\/\/doi.org\/10.1038\/leu.2017.102.","journal-title":"Leukemia"},{"key":"2494_CR21","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-020-01355-z","volume":"20","author":"Y Peng","year":"2020","unstructured":"Peng Y, Wu D, Li F, Zhang P, Feng Y, He A. Identification of key biomarkers associated with cell adhesion in multiple myeloma by integrated bioinformatics analysis. Cancer Cell Int. 2020;20:262. https:\/\/doi.org\/10.1186\/s12935-020-01355-z.","journal-title":"Cancer Cell Int"},{"key":"2494_CR22","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1182\/blood-2018-09-825331","volume":"133","author":"C Pawlyn","year":"2019","unstructured":"Pawlyn C, Davies FE. Toward personalized treatment in multiple myeloma based on molecular characteristics. Blood. 2019;133:660\u201375. https:\/\/doi.org\/10.1182\/blood-2018-09-825331.","journal-title":"Blood"},{"key":"2494_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108016","volume":"99","author":"Q Cheng","year":"2021","unstructured":"Cheng Q, Zhao F, Zhang B, Zhang Y, Cai L, Qiao B, et al. Prognostic nomogram incorporating cytokines for overall survival in patients with newly diagnosed multiple myeloma. Int Immunopharmacol. 2021;99:108016. https:\/\/doi.org\/10.1016\/j.intimp.2021.108016.","journal-title":"Int Immunopharmacol"},{"issue":"2","key":"2494_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13020217","volume":"13","author":"A Garc\u00eda-Ortiz","year":"2021","unstructured":"Garc\u00eda-Ortiz A, Rodr\u00edguez-Garc\u00eda Y, Encinas J, et al. The role of tumor microenvironment in multiple myeloma development and progression. Cancers (Basel). 2021;13(2):217. https:\/\/doi.org\/10.3390\/cancers13020217.","journal-title":"Cancers (Basel)"},{"issue":"8","key":"2494_CR25","doi-asserted-by":"publisher","first-page":"3148","DOI":"10.1182\/blood-2003-06-1984","volume":"103","author":"J Moreaux","year":"2004","unstructured":"Moreaux J, Legouffe E, Jourdan E, et al. BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood. 2004;103(8):3148\u201357. https:\/\/doi.org\/10.1182\/blood-2003-06-1984.","journal-title":"Blood"},{"issue":"25","key":"2494_CR26","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.1182\/blood-2016-01-691162","volume":"127","author":"YT Tai","year":"2016","unstructured":"Tai YT, Acharya C, An G, et al. APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood. 2016;127(25):3225\u201336. https:\/\/doi.org\/10.1182\/blood-2016-01-691162.","journal-title":"Blood"},{"issue":"9","key":"2494_CR27","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11092513","volume":"11","author":"V Desantis","year":"2022","unstructured":"Desantis V, Savino FD, Scaringella A, Potenza MA, Nacci C, Frassanito MA, et al. The leading role of the immune microenvironment in multiple myeloma: a new target with a great prognostic and clinical value. J Clin Med. 2022;11(9):2513. https:\/\/doi.org\/10.3390\/jcm11092513.","journal-title":"J Clin Med"},{"issue":"1","key":"2494_CR28","doi-asserted-by":"publisher","DOI":"10.1186\/s43556-024-00188-w","volume":"5","author":"Q Lu","year":"2024","unstructured":"Lu Q, Yang D, Li H, Niu T, Tong A. Multiple myeloma: signaling pathways and targeted therapy. Mol Biomed. 2024;5(1):25. https:\/\/doi.org\/10.1186\/s43556-024-00188-w.","journal-title":"Mol Biomed"},{"issue":"3","key":"2494_CR29","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1002\/stem.5530090303","volume":"9","author":"T Hirano","year":"1991","unstructured":"Hirano T. Interleukin 6 (IL-6) and its receptor: their role in plasma cell neoplasias. Int J Cell Cloning. 1991;9(3):166\u201384. https:\/\/doi.org\/10.1002\/stem.5530090303.","journal-title":"Int J Cell Cloning"},{"issue":"4","key":"2494_CR30","first-page":"546","volume":"11","author":"S Barill\u00e9","year":"2000","unstructured":"Barill\u00e9 S, Bataille R, Amiot M. The role of interleukin-6 and interleukin-6\/interleukin-6 receptor-alpha complex in the pathogenesis of multiple myeloma. Eur Cytokine Netw. 2000;11(4):546\u201351","journal-title":"Eur Cytokine Netw"},{"issue":"8","key":"2494_CR31","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1016\/j.ajpath.2016.04.003","volume":"186","author":"AB Herrero","year":"2016","unstructured":"Herrero AB, Garc\u00eda-G\u00f3mez A, Garayoa M, Corchete LA, Hern\u00e1ndez JM, San Miguel J, et al. Effects of IL-8 Up-Regulation on Cell Survival and Osteoclastogenesis in Multiple Myeloma. Am J Pathol. 2016;186(8):2171\u201382. https:\/\/doi.org\/10.1016\/j.ajpath.2016.04.003","journal-title":"Am J Pathol"},{"key":"2494_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2020.155358","volume":"138","author":"J Gu","year":"2021","unstructured":"Gu J, Huang X, Zhang Y, Bao C, Zhou Z, Jin J. Cytokine profiles in patients with newly diagnosed multiple myeloma: Survival is associated with IL-6 and IL-17A levels. Cytokine. 2021;138:155358. https:\/\/doi.org\/10.1016\/j.cyto.2020.155358","journal-title":"Cytokine"},{"key":"2494_CR33","doi-asserted-by":"publisher","unstructured":"Dong M, Zhang J, Chen Q, He D, Yan H, Zheng G, et al. High serum IL-17A is associated with bone destruction in newly diagnosed multiple myeloma patients. Front Oncol. 2022;31(12):936670. https:\/\/doi.org\/10.3389\/fonc.2022.936670.PMID:36119497;PMCID:PMC9471080.","DOI":"10.3389\/fonc.2022.936670.PMID:36119497;PMCID:PMC9471080"},{"issue":"8","key":"2494_CR34","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1016\/j.tranon.2019.04.023","volume":"12","author":"S Wang","year":"2019","unstructured":"Wang S, Ma Y, Wang X, Jiang J, Zhang C, Wang X, et al. IL-17A increases multiple myeloma cell viability by positively regulating Syk expression. Transl Oncol. 2019;12(8):1086\u201391. https:\/\/doi.org\/10.1016\/j.tranon.2019.04.023.","journal-title":"Transl Oncol"},{"key":"2494_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2020.155271","volume":"136","author":"S Jasrotia","year":"2020","unstructured":"Jasrotia S, Gupta R, Sharma A, Halder A, Kumar L. Cytokine profile in multiple myeloma. Cytokine. 2020;136:155271. https:\/\/doi.org\/10.1016\/j.cyto.2020.155271.","journal-title":"Cytokine"},{"issue":"3\u20134","key":"2494_CR36","doi-asserted-by":"publisher","first-page":"215","DOI":"10.3109\/10428199509059610","volume":"18","author":"A Palumbo","year":"1995","unstructured":"Palumbo A, Bruno B, Boccadoro M, Pileri A. Interferon-gamma in multiple myeloma. Leuk Lymphoma. 1995;18(3\u20134):215\u20139. https:\/\/doi.org\/10.3109\/10428199509059610","journal-title":"Leuk Lymphoma"},{"issue":"6","key":"2494_CR37","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1002\/jlb.66.6.981","volume":"66","author":"G Cook","year":"1999","unstructured":"Cook G, Campbell JD, Carr CE, Boyd KS, Franklin IM. Transforming growth factor beta from multiple myeloma cells inhibits proliferation and IL-2 responsiveness in T lymphocytes. J Leukoc Biol. 1999;66(6):981\u20138. https:\/\/doi.org\/10.1002\/jlb.66.6.981","journal-title":"J Leukoc Biol"},{"issue":"1","key":"2494_CR38","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1080\/10245330310001652437","volume":"9","author":"H Murakami","year":"2004","unstructured":"Murakami H, Ogawara H, Hiroshi H. Th1\/Th2 cells in patients with multiple myeloma. Hematology. 2004;9(1):41\u20135. https:\/\/doi.org\/10.1080\/10245330310001652437.","journal-title":"Hematology"},{"issue":"4","key":"2494_CR39","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1182\/blood-2005-03-1080","volume":"106","author":"LA Ehrlich","year":"2005","unstructured":"Ehrlich LA, Chung HY, Ghobrial I, Choi SJ, Morandi F, Colla S, et al. IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma. Blood. 2005;106(4):1407\u201314. https:\/\/doi.org\/10.1182\/blood-2005-03-1080","journal-title":"Blood"},{"issue":"6","key":"2494_CR40","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/s0889-8588(05)70115-5","volume":"13","author":"JA Lust","year":"1999","unstructured":"Lust JA, Donovan KA. The role of interleukin-1 beta in the pathogenesis of multiple myeloma. Hematol Oncol Clin North Am. 1999;13(6):1117\u201325. https:\/\/doi.org\/10.1016\/s0889-8588(05)70115-5","journal-title":"Hematol Oncol Clin North Am"},{"issue":"4","key":"2494_CR41","first-page":"513","volume":"49","author":"Y Chang","year":"2019","unstructured":"Chang Y, Xing X, Jiang Y, Shi X, Xu Y, Li A, et al. Serum Interleukin-9 Concentration Is Associated with the Hemoglobin Level and Renal Function in Patients with Multiple Myeloma. Ann Clin Lab Sci. 2019;49(4):513\u20138","journal-title":"Ann Clin Lab Sci"},{"issue":"1","key":"2494_CR42","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-013-0778-2","volume":"31","author":"G Tsirakis","year":"2014","unstructured":"Tsirakis G, Roussou P, Pappa CA, Kolovou A, Vasilokonstantaki C, Miminas I, et al. Increased serum levels of MIP-1alpha correlate with bone disease and angiogenic cytokines in patients with multiple myeloma. Med Oncol. 2014;31(1):778. https:\/\/doi.org\/10.1007\/s12032-013-0778-2.","journal-title":"Med Oncol"},{"key":"2494_CR43","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/bs.ircmb.2024.08.003","volume":"391","author":"Q Fernandes","year":"2025","unstructured":"Fernandes Q, Ansari AW, Makni-Maalej K, Merhi M, Dermime S, Ahmad A, et al. Interleukin 10: Bridging the chasms in the immune landscape of multiple myeloma. Int Rev Cell Mol Biol. 2025;391:199\u2013222. https:\/\/doi.org\/10.1016\/bs.ircmb.2024.08.003","journal-title":"Int Rev Cell Mol Biol"},{"issue":"3","key":"2494_CR44","doi-asserted-by":"publisher","first-page":"257","DOI":"10.4103\/tcmj.tcmj_141_20","volume":"33","author":"CD Liu","year":"2020","unstructured":"Liu CD, Chang CC, Huang WH. The perspectives of interleukin-10 in the pathogenesis and therapeutics of multiple myeloma. Tzu Chi Med J. 2020;33(3):257\u201362. https:\/\/doi.org\/10.4103\/tcmj.tcmj_141_20.","journal-title":"Tzu Chi Med J"},{"key":"2494_CR45","doi-asserted-by":"publisher","first-page":"4545","DOI":"10.2147\/OTT.S324810","volume":"14","author":"J Xu","year":"2021","unstructured":"Xu J, Gao L, Yan M, Wang B, Song Z, Liu H, et al. Potential role of pleural fluid cytokine profile in myelomatous pleural effusions. OncoTargets Ther. 2021;14:4545\u201350. https:\/\/doi.org\/10.2147\/OTT.S324810.","journal-title":"OncoTargets Ther"},{"issue":"10","key":"2494_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2012-4","volume":"10","author":"R Xu","year":"2019","unstructured":"Xu R, Li Y, Yan H, Zhang E, Huang X, Chen Q, et al. CCL2 promotes macrophages-associated chemoresistance via MCPIP1 dual catalytic activities in multiple myeloma. Cell Death Dis. 2019;10(10):781. https:\/\/doi.org\/10.1038\/s41419-019-2012-4.","journal-title":"Cell Death Dis"},{"key":"2494_CR47","doi-asserted-by":"crossref","unstructured":"Reglodi D, Tamas A, Pituitary Adenylate Cyclase Activating Polypeptide-PACAP, 1st ed.; Springer: Cham, Switzerland, 2016; ISBN 978\u20133\u2013319\u201335135\u20133.","DOI":"10.1007\/978-3-319-35135-3"},{"key":"2494_CR48","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1007\/s12031-018-1150-y","volume":"66","author":"C Abad","year":"2018","unstructured":"Abad C, Tan YV. Immunomodulatory roles of PACAP and VIP: lessons from knockout mice. J Mol Neurosci. 2018;66:102\u201313.","journal-title":"J Mol Neurosci"},{"key":"2494_CR49","doi-asserted-by":"publisher","first-page":"301","DOI":"10.2170\/jjphysiol.48.301","volume":"48","author":"A Arimura","year":"1998","unstructured":"Arimura A. Perspectives on pituitary adenylate cyclase activating polypeptide (PACAP) in the neuroendocrine, endocrine, and nervous systems. Jpn J Physiol. 1998;48:301\u201331.","journal-title":"Jpn J Physiol"},{"key":"2494_CR50","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1016\/j.peptides.2007.04.026","volume":"28","author":"M Laburthe","year":"2007","unstructured":"Laburthe M, Couvineau A, Tan V. Class II G protein-coupled receptors for VIP and PACAP: structure, models of activation and pharmacology. Peptides. 2007;28:1631\u20139.","journal-title":"Peptides"},{"key":"2494_CR51","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1530\/EJE-08-0911","volume":"160","author":"R Borzsei","year":"2009","unstructured":"Borzsei R, Mark L, Tamas A, et al. Presence of pituitary adenylate cyclase activating polypeptide-38 in human plasma and milk. Eur J Endocrinol. 2009;160:561\u20135.","journal-title":"Eur J Endocrinol"},{"key":"2494_CR52","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1182\/blood-2005-03-1186","volume":"107","author":"A Arimura","year":"2006","unstructured":"Arimura A, Li M, Batuman V. Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury. Blood. 2006;107:661\u20138.","journal-title":"Blood"},{"key":"2494_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1196\/annals.1317.093","volume":"1070","author":"A Arimura","year":"2006","unstructured":"Arimura A, Li M, Batuman V. Treatment of renal failure associated with multiple myeloma and other diseases by PACAP-38. Ann N Y Acad Sci. 2006;1070:1\u20134.","journal-title":"Ann N Y Acad Sci"},{"key":"2494_CR54","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.regpep.2007.09.012","volume":"145","author":"M Li","year":"2008","unstructured":"Li M, Maderdrut JL, Lertora JJ, et al. Renoprotection by pituitary adenylate cyclase-activating polypeptide in multiple myeloma and other kidney diseases. Regul Pept. 2008;145:24\u201332.","journal-title":"Regul Pept"},{"key":"2494_CR55","doi-asserted-by":"publisher","first-page":"8796","DOI":"10.1158\/0008-5472.CAN-05-2809","volume":"66","author":"M Li","year":"2006","unstructured":"Li M, Cortez S, Nakamachi T, et al. Pituitary adenylate cyclase-activating polypeptide is a potent inhibitor of the growth of light chain-secreting human multiple myeloma cells. Cancer Res. 2006;66:8796\u2013803.","journal-title":"Cancer Res"},{"key":"2494_CR56","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1016\/j.peptides.2007.05.002","volume":"28","author":"M Li","year":"2007","unstructured":"Li M, Maderdrut JL, Lertora JJ, et al. Intravenous infusion of pituitary adenylate cyclase-activating polypeptide (PACAP) in a patient with multiple myeloma and myeloma kidney: a case study. Peptides. 2007;28:1891\u20135.","journal-title":"Peptides"},{"key":"2494_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctarc.2021.100494","volume":"29","author":"A Visram","year":"2021","unstructured":"Visram A, Kourelis TV. Aging-associated immune system changes in multiple myeloma: the dark side of the moon. Cancer Treat Res Commun. 2021;29:100494. https:\/\/doi.org\/10.1016\/j.ctarc.2021.100494.","journal-title":"Cancer Treat Res Commun"},{"issue":"12","key":"2494_CR58","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009462","volume":"12","author":"F Ullrich","year":"2024","unstructured":"Ullrich F, Br\u00f6ckelmann PJ, Turki AT, Khan AM, Chiru ED, Vetter M, et al. Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma. J Immunother Cancer. 2024;12(12):e009462. https:\/\/doi.org\/10.1136\/jitc-2024-009462.","journal-title":"J Immunother Cancer"},{"issue":"10","key":"2494_CR59","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.trecan.2020.05.006","volume":"6","author":"DA Alagpulinsa","year":"2020","unstructured":"Alagpulinsa DA, Szalat RE, Poznansky MC, Shmookler Reis RJ. Genomic instability in multiple myeloma. Trends Cancer. 2020;6(10):858\u201373. https:\/\/doi.org\/10.1016\/j.trecan.2020.05.006.","journal-title":"Trends Cancer"}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-026-02494-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11357-026-02494-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-026-02494-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:56:07Z","timestamp":1789196167000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11357-026-02494-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,12]]},"references-count":59,"alternative-id":["2494"],"URL":"https:\/\/doi.org\/10.1007\/s11357-026-02494-3","relation":{},"ISSN":["2509-2723"],"issn-type":[{"value":"2509-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,12]]},"assertion":[{"value":"4 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All human sample collections were carried out according to a protocol approved by the Institutional Ethics Committee of University of P\u00e9cs (PTE KK 6383) and followed the Declaration of Helsinki and ICH GCP Guidelines to protect the rights of human subjects. In all cases, we obtained informed consent from the volunteers.","order":2,"name":"Ethics","label":"Institutional review board statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from all subjects involved in the study.","order":3,"name":"Ethics","label":"Informed consent statement","group":{"name":"EthicsHeading","label":"Declarations"}}]}}