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

J Head Trauma Rehabil. 2015 Nov-Dec;30(6):369-81. doi: 10.1097/HTR.0000000000000067.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Academic Medical Centers
  • Adult
  • Biomarkers / blood
  • Brain Injuries / blood*
  • Brain Injuries / complications*
  • Brain Injuries / diagnosis
  • Brain Injuries / therapy
  • Case-Control Studies
  • Chronic Disease
  • Confidence Intervals
  • Cytokines / blood
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glasgow Coma Scale
  • Humans
  • Inflammation / blood*
  • Inflammation / etiology
  • Inflammation / mortality
  • Inflammation / physiopathology
  • Injury Severity Score
  • Interleukins / blood*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Pennsylvania
  • Prospective Studies
  • Risk Assessment
  • Survival Analysis
  • Time Factors
  • Trauma Centers
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha

Substances

  • Biomarkers
  • Cytokines
  • Interleukins
  • Tumor Necrosis Factor-alpha