Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Abstract

A unique cohort of military personnel exposed to isolated blast was studied to explore acute peripheral cytokine levels, with the aim of identifying blast-specific biomarkers. Several cytokines, including interleukin (IL) 6, IL-10 and tumor necrosis factor alpha (TNFα) have been linked to pre-clinical blast exposure, but remained unstudied in clinical blast exposure. To address this gap, blood samples from 62 military personnel were obtained at baseline, and daily, during a 10-day blast-related training program; changes in the peripheral concentrations of IL-6, IL-10 and TNFα were evaluated using an ultrasensitive assay. Two groups of trainees were matched on age, duration of military service, and previous history of blast exposure(s), resulting in moderate blast cases and no/low blast controls. Blast exposures were measured using helmet sensors that determined the average peak pressure in pounds per square inch (psi). Moderate blast cases had significantly elevated concentrations of IL-6 (F1,60 =18.81, p < 0.01) and TNFα (F1,60 =12.03, p < 0.01) compared to no/low blast controls; levels rebounded to baseline levels the day after blast. On the day of the moderate blast exposure, the extent of the overpressure (psi) in those exposed correlated with IL-6 (r = 0.46, p < 0.05) concentrations. These findings indicate that moderate primary blast exposure results in changes, specifically acute and transient increases in peripheral inflammatory markers which may have implications for neuronal health.

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

“…Clinical research on serum cytokine levels and TBI severity (mild, moderate, and severe) has mainly centered on the acute phase following a TBI, defined as 1-7 days posttrauma [23,25,26]. Circulating levels of a number of inflammatory cytokines such as interleukin-1β (IL-1 β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) have been examined [16,18,[27][28][29][30].…”

“…There is a paucity of human data on the systemic cytokine immune response during the acute phase [26,44] or during later time points specific for bTBI [45]. Better characterization of the cytokine response in peripheral serum during recovery post-bTBI would help clarify the systemic inflammatory processes during the chronic phase, may provide better monitoring of the recovery or rehabilitative period, and may possibly identify and evaluate therapeutic interventions [46][47][48].…”

Lack of chronic neuroinflammation in the absence of focal hemorrhage in a rat model of low-energy blast-induced TBI

“…The hippocampus and prefrontal cortex (PFC) also contained increased numbers of apoptotic cells (TUNEL-positive) and elevated levels of GFAP, S100β, Iba1, VEGF, IL-6, IFN-γ, and phosphorylated tau [32]. In humans, 35-to 81-kPa blast exposures result in increased levels of IL-6 and TNF-α in the serum that were maintained for 24 h [18].…”

Systemic Inflammation Persists the First Year after Mild Traumatic Brain Injury: Results from the Prospective Trondheim Mild Traumatic Brain Injury Study

“…This is in contrast to studies showing acute but transient increase of plasma cytokines in mTBI. In a study of blast-exposed military personnel, cytokines IL-6 and TNF returned to baseline levels within hours, 27 whereas in sportsrelated concussion cytokines IL-6 and IL-12 returned to baseline within 7 days. 9 In children with concussion, TNF, IL-6, IL-1b, IL-10, and several neuronal damage plasma markers returned to baseline within days, whereas IL-8 remained increased for 3 months.…”