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

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- A nd anti-inflammatory cytokines, measured both pre- A nd 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.