Interleukin-6 is associated with acute concussion in military combat personnel

Abstract

Background: Concussion is the most common type of TBI, yet reliable objective measures related to these injuries and associated recovery processes remain elusive, especially in military personnel. The purpose of this study was to characterize the relationship between cytokines and recovery from acute brain injury in active duty service members. Inflammatory cytokines (IL-6, IL-10, and TNFα) were measured acutely in blood samples within 8 h following a medically diagnosed concussion and then 24 h later. Methods: Participants (n = 94) were categorized into two groups: 1) military personnel who sustained providerdiagnosed concussion, without other major medical diagnosis (n = 45) and 2) healthy control participants in the same deployment environment who did not sustain concussion or other illness or injuries (n = 49). IL-6, IL-10, and TNFα concentrations were measured using an ultrasensitive single-molecule enzyme-linked immunosorbent assay. Differences in cytokine levels between concussed and healthy groups were evaluated at two time points (time point 1 ≤ 8 h after injury; time point 2 = 24 h following time point 1). Results: At time point 1, IL-6 median (IQR) concentrations were 2.62 (3.62) in the concussed group, which was greater compared to IL-6 in the healthy control group (1.03 (0.90); U = 420.00, z = − 5.12, p < 0.001). Compared to healthy controls, the concussed group did not differ at time point 1 in IL-10 or TNFα concentrations (p's > 0.05). At time point 2, no differences were detected between concussed and healthy controls for IL-6, IL-10, or TNFα (p's > 0.05). The median difference between time points 1 and 2 were compared between the concussed and healthy control groups for IL-6, IL-10, and TNFα. Change in IL-6 across time was greater for the concussed group than healthy control (− 1.54 (3.12); U = 315.00, z = − 5.96, p < 0.001), with no differences between groups in the change of IL-10 or TNFα (p's > 0.05). Conclusion: Reported here is a significant elevation of IL-6 levels in concussed military personnel less than 8 h following injury. Future studies may examine acute and chronic neurological symptomology associated with inflammatory cytokine levels, distinguish individuals at high risk for developing neurological complications, and identify underlying biological pathways to mitigate inflammation and improve outcomes.

Feasibility and preliminary efficacy for morning bright light therapy to improve sleep and plasma biomarkers in US Veterans with TBI. A prospective, open-label, single-arm trial

“…We found reductions in pro-inflammatory cytokines IL-6 and TNF-ɑ, and no change in the anti-inflammatory cytokine IL-10. These results are also consistent with existing literature, as other studies have reported improvements in pro-inflammatory cytokines with improved sleep, including treatment of sleep apnea [ 60 , 78 ].…”

“…Furthermore, one of the 4 biomarkers in the 4-plex, UCHL1, was unable to be included in our analyses. However, NfL and tau are both widely accepted markers of neuronal injury [ 60 , 76 , 77 ]. Further, despite the small sample size, peripheral markers of neuronal injury and neuroinflammation such as NfL and tau still showed trends towards statistical significance in directions consistent with the existing literature.…”

“…Plasma samples were sent to the NIH NINR Biomarker Core Laboratory (PI: J.M.G.) for 4-plex and 3-plex immunoassays (exploratory outcomes) using an ultrasensitive single-molecule enzyme-linked immunosorbent assay via Simoa ™ technology (Quanterix, Lexington, MA, USA) [ 60 – 62 ]. The 4-plex measured concentrations of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), tau, and ubiquitin C-terminal hydrolase-L1 (UCHL1) [ 63 ].…”

Correlation between Mild Traumatic Brain Injury-Induced Inflammatory Cytokines and Emotional Symptom Traits: A Systematic Review

“…IL-6 acts as a regulator of inflammatory procedures by inducing either a pro- or anti-inflammatory response [ 11 ]. IL-6 levels are typically upregulated shortly after a mTBI event [ 21 , 22 ], and can remain elevated for weeks or months following such an injury [ 18 , 23 ]. Acutely elevated IL-6 levels are associated with greater symptom duration and severity in mTBI [ 17 , 21 , 38 ].…”

“…Similarly, our previous review has demonstrated that depression and anxiety are associated with elevated TNF-α, IL-6, IFN-α, and C-Reactive Protein (CRP) levels [ 9 ]. Overall, the most common systemic cytokines associated with mTBI include IL-6 [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ], TNF-α [ 20 , 23 , 24 , 25 ], IL-10 [ 20 , 26 ], IL-1β [ 19 , 20 ], Interleukin-8 (IL-8) [ 20 , 25 ], Interferon Gamma (IFN-γ) [ 20 , 25 ], Interleukin-1RA (IL-1RA) [ 17 , 21 ], Interleukin-4 (IL-4) [ 20 ], and C–C motif chemokine ligand 2 (CCL2) [ 19 , 27 ].…”