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Chronic Inflammation After Severe Traumatic Brain Injury: Characterization and Associations With Outcome at 6 and 12 Months Postinjury

Kumar, Raj G. MPH; Boles, Jennifer A. BS; Wagner, Amy K. MD

Section Editor(s): Caplan, Bruce PhD, ABPP; Bogner, Jennifer PhD, ABPP; Brenner, Lisa PhD, ABPP

Journal of Head Trauma Rehabilitation: November/December 2015 - Volume 30 - Issue 6 - p 369–381
doi: 10.1097/HTR.0000000000000067
Original Articles

Objective: Examine associations between chronic inflammatory profiles and outcome 6 to 12 months following severe traumatic brain injury (TBI).

Setting: University-affiliated level 1 trauma center and community.

Participants: Adults with severe TBI (n = 87); healthy controls (n = 7).

Design: Prospective cohort study.

Main Measures: Glasgow Outcome Scale; serum cytokines (interleukin [IL]-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, tumor necrosis factor α), 2 weeks to 3 months, 4- to 6-month averages, 6- and 12-month levels.

Results: Serum levels of IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor α were elevated over 3 months following TBI. Multivariate analysis showed that increased cytokine load score was associated with a 1.21 (95% confidence interval, 1.06-1.38) and 1.18 (95% confidence interval, 1.02-1.37) increase in odds of unfavorable Glasgow Outcome Scale score at 6 and 12 months, respectively. Also, elevated IL-6/IL-10 ratios were associated with increased odds of unfavorable outcomes at 6 months (adjusted odds ratio = 1.76; 95% confidence interval, 1.08-2.88).

Conclusions: Chronic inflammation has not been well characterized following TBI. Our subacute cytokine load score classifies individuals at risk for unfavorable outcomes following injury. Higher proinflammatory burden with IL-6, relative to the anti-inflammatory marker IL-10, is significantly associated with outcome. Further research should examine whether inflammatory genes and other inflammatory biomarkers affect risk for unfavorable outcomes and TBI complications.

Department of Physical Medicine and Rehabilitation (Mr Kumar, Ms Boles, and Dr Wagner), Center for Neuroscience (Dr Wagner), and Safar Center for Resuscitation Research (Dr Wagner), University of Pittsburgh, Pittsburgh, Pennsylvania.

Corresponding Author: Amy K. Wagner, MD, Department of Physical Medicine & Rehabilitation, and Rehabilitation Research, Safar Center for Resuscitation Research, University of Pittsburgh, 3471 Fifth Ave, Ste 202, Pittsburgh, PA 15213 (

This work was supported in part by CDC: R49 CCR 323155, DOD: W81XWH-071-0701, NIDRR H133A120087, University of Pittsburgh Women's Studies Faculty Research Fund.

The authors thank the UPMC Trauma Registry for their support with data collection. The authors also thank the University of Pittsburgh Cancer Institute for their support with performing luminex assays.

The authors declare no conflicts of interest.

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