{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:11:20Z","timestamp":1791353480908,"version":"4.3.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>To identify new intervention targets, we explored the correlation between cytokines and the development of refractory status epilepticus (RSE) in patients with severe viral encephalitis (SVE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined the characteristics of 14 cytokines in the cerebrospinal fluid (CSF) and serum, analyzing their correlation with acute symptomatic seizures and prognosis. Furthermore, we conducted a dynamic analysis of differences and correlations in the expression of cytokines among patients with SVE without seizures, those with controlled seizures, and those with RSE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 161 patients with SVE; the incidence of seizures was 55.2%, and the mortality rate was 5.5%. Notably, 18.9% of these patients developed RSE, with a mortality rate of 20%. During the early stage of SVE, CSF interleukin (IL)-6 and IL-8 levels were significantly higher, declining over time and affecting the prognosis. CSF IL-6 and IL-8 levels were significantly elevated in the RSE group compared to patients without seizures and with controlled seizures, decreasing gradually and independently of serum cytokine levels. CSF IL-8 and age were independent risk factors for RSE, with clinical utility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients with SVE exhibit intrathecal cytokine storms, primarily characterized by elevated levels of IL-6 and IL-8, which influence prognosis. The strong and persistent hyperinflammation underscored by CSF IL-6 and IL-8 is associated with the occurrence and development of RSE; thus, CSF IL-8 and age are independent risk factors for SVE with RSE, indicating potential anti-inflammatory intervention targets.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1528763","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T06:51:24Z","timestamp":1739170284000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Cerebrospinal fluid and serum cytokine profiles in severe viral encephalitis with implications for refractory status epilepticus: a retrospective observational study"],"prefix":"10.3389","volume":"16","author":[{"given":"Peipei","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruirui","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuling","family":"Zang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junshuang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruike","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiping","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjin","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfang","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1212\/WNL.0b013e3182a2cc6d","article-title":"Predictors of outcome in acute encephalitis","volume":"81","author":"Thakur","year":"2013","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13121","article-title":"A definition and classification of status epilepticus\u2013Report of the ILAE Task Force on Classification of Status Epilepticus","volume":"56","author":"Trinka","year":"2015","journal-title":"Epilepsia"},{"key":"B3","doi-asserted-by":"publisher","first-page":"15357597219 99670","DOI":"10.1177\/1535759721999670","article-title":"Treatment of super-refractory status epilepticus: A review","volume":"21","author":"Ochoa","year":"2021","journal-title":"Epilepsy Curr"},{"key":"B4","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13054-017-1661-x","article-title":"Predictors of hospital and one-year mortality in intensive care patients with refractory status epilepticus: a population-based study","volume":"21","author":"Kantanen","year":"2017","journal-title":"Crit Care"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00134-023-07263-w","article-title":"Status epilepticus in the ICU","volume":"50","author":"Rossetti","year":"2024","journal-title":"Intensive Care Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1212\/nxi.0000000000200259","article-title":"Single-cell transcriptomic analyses of brain parenchyma in patients with new-onset refractory status epilepticus (NORSE)","volume":"11","author":"Hanin","year":"2024","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B7","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/epi.13785","article-title":"Neuroinflammation in epileptogenesis: insights and translational perspectives from new models of epilepsy","author":"Barker-Haliski","year":"2017","journal-title":"Epilepsia"},{"key":"B8","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/nrneurol.2010.178","article-title":"The role of inflammation in epilepsy","volume":"7","author":"Vezzani","year":"2011","journal-title":"Nat Rev Neurol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s12974-018-1192-7","article-title":"The role of inflammation in the development of epilepsy","volume":"15","author":"Rana","year":"2018","journal-title":"J Neuroinflammation"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.826603","article-title":"The comparison of inflammatory cytokines (IL-6 and IL-18) and immune cells in Japanese encephalitis patients with different progression","volume":"12","author":"Zhou","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0273920","article-title":"Cytokines and chemokines profile in encephalitis patients: A meta-analysis","volume":"17","author":"Soltani Khaboushan","year":"2022","journal-title":"PloS One"},{"key":"B12","doi-asserted-by":"publisher","first-page":"6446","DOI":"10.3390\/ijms23126446","article-title":"Immunity, ion channels and epilepsy","volume":"23","author":"Chen","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad066","article-title":"Cytotoxic T cells and plasma cells dominate early in temporal lobe epilepsy with GAD antibodies","volume":"146","author":"Thaler","year":"2023","journal-title":"Brain"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2015.07.021","article-title":"Thyroid hormones: possible roles in epilepsy pathology","volume":"31","author":"Tamijani","year":"2015","journal-title":"Seizure"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit458","article-title":"Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium","volume":"57","author":"Venkatesan","year":"2013","journal-title":"Cli Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1111\/j.1468-1331.2010.02970.x","article-title":"Viral meningoencephalitis: a review of diagnostic methods and guidelines for management","volume":"17","author":"Steiner","year":"2010","journal-title":"Eur J Neurol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s13052-023-01411-0","article-title":"The efficacy of haemoperfusion combined with continuous venovenous haemodiafiltration in the treatment of severe viral encephalitis in children","volume":"49","author":"Zhao","year":"2023","journal-title":"Ital J Pediatr"},{"key":"B18","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1111\/j.1528-1167.2012.03615.x","article-title":"Seizures and encephalitis: clinical features, management, and potential pathophysiologic mechanisms","author":"Michael","year":"2012","journal-title":"Epilepsia"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad306","article-title":"State of the art: acute encephalitis","volume":"77","author":"Bloch","year":"2023","journal-title":"Clin Infect Dis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318f11d65","article-title":"Challenge of the unknown. A systematic review of acute encephalitis in non-outbreak situations","volume":"75","author":"Granerod","year":"2010","journal-title":"Neurology"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803396","article-title":"Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis","volume":"380","author":"Wilson","year":"2019","journal-title":"N Engl J Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.24140","article-title":"Analysis of serum levels of cytokines, chemokines, growth factors, and monoamine neurotransmitters in patients with tick-borne encephalitis: identification of novel inflammatory markers with implications for pathogenesis","volume":"87","author":"Palus","year":"2015","journal-title":"J Med Virol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/9782381","article-title":"Retracted: detection and diagnostic value of cytokines in serum of children with acute viral encephalitis","volume":"2023","author":"Imaging","year":"2023","journal-title":"Contrast Media Mol Imaging"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.866153","article-title":"CSF biomarkers in COVID-19 associated encephalopathy and encephalitis predict long-term outcome","volume":"13","author":"Guasp","year":"2022","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1086\/423328","article-title":"Proinflammatory cytokines and chemokines in humans with Japanese encephalitis","volume":"190","author":"Winter","year":"2004","journal-title":"J Infect Dis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1186\/s12974-016-0773-6","article-title":"Pro-epileptogenic effects of viral-like inflammation in both mature and immature brains","volume":"13","author":"Dupuis","year":"2016","journal-title":"J Neuroinflammation"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp177","article-title":"The cortical innate immune response increases local neuronal excitability leading to seizures","volume":"132","author":"Rodgers","year":"2009","journal-title":"Brain"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02725-6","article-title":"Neuroinflammation and proinflammatory cytokines in epileptogenesis","volume":"59","author":"Soltani Khaboushan","year":"2022","journal-title":"Mol Neurobiol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejphar.2007.10.049","article-title":"Cytokines and anti-cytokines as therapeutics\u2013an update","volume":"579","author":"Tayal","year":"2008","journal-title":"Eur J Pharmacol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106027","article-title":"Neuroinflammation microenvironment sharpens seizure circuit","volume":"178","author":"Villasana-Salazar","year":"2023","journal-title":"Neurobiol Dis"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1134\/S000629791703004X","article-title":"Modulating effect of cytokines on mechanisms of synaptic plasticity in the brain","volume":"82","author":"Levin","year":"2017","journal-title":"Biochemistry(Mosc)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-020-00893-8","article-title":"IL-6 receptor blockade by tocilizumab has anti-absence and anti-epileptogenic effects in the WAG\/Rij rat model of absence epilepsy","volume":"17","author":"Leo","year":"2020","journal-title":"Neurotherapeutics"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25374","article-title":"Tocilizumab treatment for new onset refractory status epilepticus","volume":"84","author":"Jun","year":"2018","journal-title":"Ann Neurol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2021.577789","article-title":"Cryptogenic new-onset refractory status epilepticus responded to anti-interleukin-6 treatment","volume":"363","author":"Wadayama","year":"2022","journal-title":"J Neuroimmunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/ana.26627","article-title":"Cytokines in new-onset refractory status epilepticus predict outcomes","volume":"94","author":"Hanin","year":"2023","journal-title":"Ann Neurol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00233.2002","article-title":"Pathophysiological roles of interleukin-8\/CXCL8 in pulmonary diseases. American journal of physiology","volume":"284","author":"Mukaida","year":"2003","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/s1074-7613(03)00174-2","article-title":"Blood monocytes consist of two principal subsets with distinct migratory properties","volume":"19","author":"Geissmann","year":"2003","journal-title":"Immunity"},{"key":"B38","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1084\/jem.20081385","article-title":"CX3CR1+ CD115+ CD135+ common macrophage\/DC precursors and the role of CX3CR1 in their response to inflammation","volume":"206","author":"Auffray","year":"2009","journal-title":"J Exp Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01907","article-title":"In vivo differentiation of human monocytes","volume":"10","author":"Coillard","year":"2019","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.celrep.2014.09.032","article-title":"Nonclassical Ly6C(-) monocytes drive the development of inflammatory arthritis in mice","volume":"9","author":"Misharin","year":"2014","journal-title":"Cell Rep"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jacc.2013.09.019","article-title":"The role of monocytes in angiogenesis and atherosclerosis","volume":"63","author":"Jaipersad","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp144","article-title":"CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system","volume":"132","author":"Mildner","year":"2009","journal-title":"Brain"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1172\/62636","article-title":"Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS","volume":"122","author":"Butovsky","year":"2012","journal-title":"J Clin Invest"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.3390\/cells10081860","article-title":"Tuning monocytes and macrophages for personalized therapy and diagnostic challenge in rheumatoid arthritis","volume":"10","author":"Roszkowski","year":"2021","journal-title":"Cells"},{"key":"B45","doi-asserted-by":"publisher","first-page":"4072","DOI":"10.3390\/cells11244072","article-title":"Innate immune memory in monocytes and macrophages: the potential therapeutic strategies for atherosclerosis","volume":"11","author":"Guo","year":"2022","journal-title":"Cells"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080421","article-title":"Ly6c+ \u201cinflammatory monocytes\u201d are microglial precursors recruited in a pathogenic manner in West Nile virus encephalitis","volume":"205","author":"Getts","year":"2008","journal-title":"J Exp Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-246","article-title":"Targeted blockade in lethal West Nile virus encephalitis indicates a crucial role for very late antigen (VLA)-4-dependent recruitment of nitric oxide-producing macrophages","volume":"9","author":"Getts","year":"2012","journal-title":"J Neuroinflammation"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-270","article-title":"Inflammatory monocytes and the pathogenesis of viral encephalitis","volume":"9","author":"Terry","year":"2012","journal-title":"J Neuroinflammation"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20220621","article-title":"Impaired immune response drives age-dependent severity of COVID-19","volume":"219","author":"Beer","year":"2022","journal-title":"J Exp Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1528763\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T06:51:26Z","timestamp":1739170286000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1528763\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,10]]},"references-count":49,"alternative-id":["10.3389\/fimmu.2025.1528763"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1528763","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,10]]},"article-number":"1528763"}}