{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:36:49Z","timestamp":1786534609493,"version":"build-2736575974"},"reference-count":45,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["U01NS086090"],"award-info":[{"award-number":["U01NS086090"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"ERA-NET NEURON Cofund","award":["MR\/R004528\/1"],"award-info":[{"award-number":["MR\/R004528\/1"]}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"crossref","award":["Pilot Grant 2021"],"award-info":[{"award-number":["Pilot Grant 2021"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Neurotrauma Reports"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Inflammation following traumatic brain injury (TBI) may contribute to long-term morbidity. We aimed to characterize plasma interleukin-6 (IL6) trajectory after TBI and assess associations with imaging, biomarkers, and outcomes. Secondary analysis of three prospective multicenter observational cohorts: BIO-AX-TBI (United Kingdom\/Europe), CREACTIVE (Europe), and TRACK-TBI (United States). Adults (\u226518 years) with TBI were enrolled at trauma centers, with non-TBI trauma (NTT) and non-injured controls (CON) included in BIO-AX-TBI and TRACK-TBI. Blood was obtained at acute (\u226410 days), subacute (10 days\u20136 weeks), and chronic (6 and 12 months) timepoints. IL6 was measured on OLINK\u00ae (BIO-AX-TBI, CREACTIVE) or MSD S-PLEX (TRACK-TBI) platforms. The Glasgow Outcome Scale\u2013Extended (GOS-E) assessed functional outcome at chronic time points, dichotomized as unfavorable (1\u20134) versus favorable (5\u20138). Additional outcomes included neuropsychiatric symptom scores, magnetic resonance imaging (MRI) measures (lesion volume, fractional anisotropy [FA]), and neuronal\/astroglial injury markers. BIO-AX-TBI included\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 195 TBI,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 24 NTT, and\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 89 CON; CREACTIVE included\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 1146 TBI, TRACK-TBI included\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 387 TBI,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 98 NTT, and\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 67 CON. IL6 was significantly elevated acutely in both TBI and NTT compared with CON but highest in TBI. In BIO-AX-TBI, IL6 remained elevated at 6 months (TBI median = 2.47, IQR = 1.98\u20132.87 vs. CON median = 2.13, IQR = 1.74\u20132.58; t = 2.50;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.014) and 12 months (TBI median = 2.53, IQR = 2.08\u20133.06; t = 4.11;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.001). Acute IL6 correlated with intracranial injury (GFAP; t\/\n                    <jats:italic toggle=\"yes\">z<\/jats:italic>\n                    = 5.14\u20138.14;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.001), extracranial injury (t\/\n                    <jats:italic toggle=\"yes\">z<\/jats:italic>\n                    = 3.89\u20139.08;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.005), and other plasma markers (r\n                    <jats:sub>s<\/jats:sub>\n                    = 0.2\u20130.67; false discovery rate-corrected\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.05). Higher peak IL-6 was associated with greater lesion volume (t = 2.82;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.0057) and reduced white matter FA (t = 2.47\u20132.54;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.05). Elevated subacute IL6 was associated with unfavorable GOS-E across all cohorts. No associations were observed with neuropsychiatric symptoms. Post-TBI IL6 elevation persists up to 12 months and is associated with greater tissue injury and worse outcomes, suggesting IL6 as a potential therapeutic target.\n                  <\/jats:p>","DOI":"10.1177\/2689288x261448726","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:08:38Z","timestamp":1786352918000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural History and Clinical Associations of Plasma Interleukin-6 Levels in Traumatic Brain Injury"],"prefix":"10.1177","volume":"7","author":[{"given":"Leo","family":"Layzell","sequence":"first","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftheria","family":"Kodosaki","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at University College London, London, UK."},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Sun","sequence":"additional","affiliation":[{"name":"Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Jain","sequence":"additional","affiliation":[{"name":"Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Heslegrave","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at University College London, London, UK."},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Soreq","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, London, UK."},{"name":"UK Dementia Research Institute Care Research and Technology Centre, Imperial College London and University of Surrey, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3034-6251","authenticated-orcid":false,"given":"Giovanni","family":"Nattino","sequence":"additional","affiliation":[{"name":"IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Garbero","sequence":"additional","affiliation":[{"name":"IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl A.","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil S.N.","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Moro","sequence":"additional","affiliation":[{"name":"IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Novelli","sequence":"additional","affiliation":[{"name":"IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Primo\u017e","family":"Gradi\u0161ek","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Magnoni","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at University College London, London, UK."},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK."},{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden."},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden."},{"name":"Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China."},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin W.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Center for Neurotrauma, Multiomics &amp; Biomarkers Morehouse School of Medicine, Atlanta, Georgia, USA."},{"name":"Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Health Care System Decatur, Atlanta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firas H.","family":"Kobeissy","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Center for Neurotrauma, Multiomics &amp; Biomarkers Morehouse School of Medicine, Atlanta, Georgia, USA."},{"name":"Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Health Care System Decatur, Atlanta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9694-7722","authenticated-orcid":false,"given":"John K.","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA."},{"name":"Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA."},{"name":"Brain and Spinal Injury Center, Zuckerberg San Francisco General Hospital, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ava M.","family":"Puccio","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Bertolini","sequence":"additional","affiliation":[{"name":"IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, 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