Systemic inflammation and its associations in acute moderate-severe Traumatic Brain Injury: a cross-sectional study
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Traumatic Brain Injury (TBI) triggers an acute systemic inflammatory response, which may impact outcomes. This response may interact with pre-existing factors linked to inflammation, such as age, to influence outcomes. Previous studies have typically measured few cytokines, but high-dimensional proteomic approaches can sensitively detect a broad range of inflammatory markers, to better characterise post-TBI inflammation.
We analysed plasma from BIO-AX-TBI study participants (n = 37 acute moderate–severe TBI (Mayo Criteria), n = 22 acute non-TBI trauma (NTT), n = 28 non-injured controls (CON)) using the Alamar NULISA™ panel (>200 inflammatory markers). The NTT group enabled differentiation of TBI-specific versus general injury-related responses. Inflammatory markers were correlated with plasma NFL, GFAP, total tau, UCH-L1 (Simoa®), S100B (Millipore), and subacute (10 days–6 weeks) 3T MRI measures of lesion volume and white matter injury.
Differential expression analysis identified four markers elevated specifically in TBI (VSNL1, IL1RN/IL-1Ra, GFAP, IKBKG), while other derangements reflected non-specific injury responses. Higher VSNL1 correlated with greater lesion volume (rs = 0.53) and higher IL1RN/IL-1Ra with greater white matter injury (rs = −0.66, both FDR-adjusted p < 0.05). IL33, part of the non-specific injury response was higher in participants with good (GOS-E 5–8) versus poor (GOS-E 1–4) outcomes (W = 47, FDR-adjusted p = 0.0024). Using an Elastic Net model trained on healthy controls, we show that “inflammation age” exceeded chronological age in TBI, particularly in younger participants.
In summary, acute post-TBI inflammation includes both TBI-specific and non-specific components, linked to structural brain injury and functional outcome. Age modulates the inflammatory response. VSNL1, IL1RN/IL-1Ra, and IL33 are potential mediators of post-TBI pathophysiology.
We analysed plasma from BIO-AX-TBI study participants (n = 37 acute moderate–severe TBI (Mayo Criteria), n = 22 acute non-TBI trauma (NTT), n = 28 non-injured controls (CON)) using the Alamar NULISA™ panel (>200 inflammatory markers). The NTT group enabled differentiation of TBI-specific versus general injury-related responses. Inflammatory markers were correlated with plasma NFL, GFAP, total tau, UCH-L1 (Simoa®), S100B (Millipore), and subacute (10 days–6 weeks) 3T MRI measures of lesion volume and white matter injury.
Differential expression analysis identified four markers elevated specifically in TBI (VSNL1, IL1RN/IL-1Ra, GFAP, IKBKG), while other derangements reflected non-specific injury responses. Higher VSNL1 correlated with greater lesion volume (rs = 0.53) and higher IL1RN/IL-1Ra with greater white matter injury (rs = −0.66, both FDR-adjusted p < 0.05). IL33, part of the non-specific injury response was higher in participants with good (GOS-E 5–8) versus poor (GOS-E 1–4) outcomes (W = 47, FDR-adjusted p = 0.0024). Using an Elastic Net model trained on healthy controls, we show that “inflammation age” exceeded chronological age in TBI, particularly in younger participants.
In summary, acute post-TBI inflammation includes both TBI-specific and non-specific components, linked to structural brain injury and functional outcome. Age modulates the inflammatory response. VSNL1, IL1RN/IL-1Ra, and IL33 are potential mediators of post-TBI pathophysiology.
Date Issued
2026-03-01
Date Acceptance
2026-01-11
Citation
Brain, Behavior, & Immunity - Health, 2026, 52
ISSN
2666-3546
Publisher
Elsevier
Journal / Book Title
Brain, Behavior, & Immunity - Health
Volume
52
Copyright Statement
© 2026 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Publication Status
Published
Article Number
101179
Date Publish Online
2026-01-14