Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members

J Neuroinflammation. 2020 Jan 13;17(1):20. doi: 10.1186/s12974-019-1624-z.

Abstract

Background: There is a paucity of human data on exposure to blast traumatic brain injury (bTBI) and the corresponding systemic cytokine immune response at later time points (i.e., months, years) post-injury.

Methods: We conducted a repeated measures, case-control study, examining associations of serum levels of pro- and anti-inflammatory cytokines, measured both pre- and post-deployment with having mild and moderate/severe bTBI. Utilizing serum from the Department of Defense Serum Repository cytokines were measured via an ELISA-based array for 15 cytokines. We compared pre- vs. post-levels among mild cases, moderate/severe cases, and controls and carried out case-control comparisons, using paired t- tests and generalized linear models.

Results: The average time between bTBI and post-deployment/bTBI serum among cases was 315.8 days. From pre- to post-deployment/bTBI, levels of interleukin 8 (IL-8) were decreased among both mild cases (μ = - 83.43 pg/ml; s.e. = 21.66) and moderate/severe cases (μ = - 107.67 pg/ml; s.e. = 28.74 pg/ml), while levels increased among controls (μ = 32.86 pg/ml; s.e. = 30.29). The same pattern occurred for matrix metallopeptidase 3 (MMP3), with levels decreasing for moderate/severe cases (μ = - 3369.24 pg/ml; s.e. = 1701.68) and increasing for controls (μ = 1859.60 pg/ml; s.e. = 1737.51) from pre- to post-deployment/bTBI. Evidence was also suggestive of case-control differences, from pre- to post-deployment/bTBI for interleukin 1 alpha (IL-1α), interleukin 4 (IL-4), and interleukin 6 (IL-6) among moderate/severe cases.

Conclusion: The findings of this longitudinal study indicate that in the chronic phase of bTBI, levels of IL-8 and MMP3 may be substantially lower than pre-injury. These results need confirmation in other studies, potentially those that account for treatment differences, which was not possible in our study.

Keywords: Cytokines; Inflammation; Microarray; Military; Operation Iraqi freedom; Operation enduring freedom; Protein; TBI; Traumatic brain injury.

MeSH terms

  • Adult
  • Blast Injuries / blood*
  • Blast Injuries / complications*
  • Blast Injuries / immunology
  • Brain Injuries, Traumatic / blood*
  • Brain Injuries, Traumatic / etiology*
  • Brain Injuries, Traumatic / immunology
  • Case-Control Studies
  • Cytokines / blood*
  • Female
  • Humans
  • Inflammation / blood
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Military Personnel
  • Young Adult

Substances

  • Cytokines