Natural history and clinical associations of plasma interleukin-6 levels in traumatic brain injury
Author(s)
Type
Journal Article
Abstract
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 (≥18 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 (≤10 days), subacute (10 days–6 weeks), and chronic (6 and 12 months) timepoints. IL6 was measured on OLINK® (BIO-AX-TBI, CREACTIVE) or MSD S-PLEX (TRACK-TBI) platforms. Glasgow Outcome Scale–Extended (GOS-E) assessed functional outcome at chronic timepoints, dichotomized as unfavorable (1–4) vs favorable (5–8). Additional outcomes included neuropsychiatric symptom scores, MRI measures (lesion volume, fractional anisotropy [FA]), and neuronal/astroglial injury markers.
BIO-AX-TBI included n=195 TBI, n=24 NTT, n=89 CON; CREACTIVE included n=1146 TBI, TRACK-TBI included n=387 TBI, n=98 NTT, 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=1.98-2.87 vs CON median=2.13 IQR=1.74-2.58; t=2.50; p=0.014) and 12 months (TBI median=2.53 IQR=2.08-3.06; t=4.11; p<0.001). Acute IL6 correlated with intracranial injury (GFAP; t/z=5.14–8.14; p<0.001), extracranial injury (t/z=3.89–9.08; p<0.005), and other plasma markers (rs=0.2–0.67; FDR-corrected p<0.05). Higher peak IL6 was associated with greater lesion volume (t=2.82; p=0.0057) and reduced white matter FA (t=2.47–2.54; p<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.
Secondary analysis of three prospective multicenter observational cohorts: BIO-AX-TBI (United Kingdom/Europe), CREACTIVE (Europe), and TRACK-TBI (United States). Adults (≥18 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 (≤10 days), subacute (10 days–6 weeks), and chronic (6 and 12 months) timepoints. IL6 was measured on OLINK® (BIO-AX-TBI, CREACTIVE) or MSD S-PLEX (TRACK-TBI) platforms. Glasgow Outcome Scale–Extended (GOS-E) assessed functional outcome at chronic timepoints, dichotomized as unfavorable (1–4) vs favorable (5–8). Additional outcomes included neuropsychiatric symptom scores, MRI measures (lesion volume, fractional anisotropy [FA]), and neuronal/astroglial injury markers.
BIO-AX-TBI included n=195 TBI, n=24 NTT, n=89 CON; CREACTIVE included n=1146 TBI, TRACK-TBI included n=387 TBI, n=98 NTT, 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=1.98-2.87 vs CON median=2.13 IQR=1.74-2.58; t=2.50; p=0.014) and 12 months (TBI median=2.53 IQR=2.08-3.06; t=4.11; p<0.001). Acute IL6 correlated with intracranial injury (GFAP; t/z=5.14–8.14; p<0.001), extracranial injury (t/z=3.89–9.08; p<0.005), and other plasma markers (rs=0.2–0.67; FDR-corrected p<0.05). Higher peak IL6 was associated with greater lesion volume (t=2.82; p=0.0057) and reduced white matter FA (t=2.47–2.54; p<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.
Date Issued
2026-01-01
Date Acceptance
2026-04-20
Citation
Neurotrauma Reports, 2026, 7, pp.1-14
ISSN
2689-288X
Publisher
Mary Ann Liebert
Start Page
1
End Page
14
Journal / Book Title
Neurotrauma Reports
Volume
7
Copyright Statement
ª The Author(s) 2026. Published by Mary Ann Liebert (NY), LLC. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, repro- duction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
License URL
Identifier
10.1177/2689288X261448726
Subjects
adult brain injury
IL6
interleukin 6
Publication Status
Published
Date Publish Online
2026-08-10