To determine whether inflammation is linked to sleep quality in a cross-sectional cohort of warfighters with and without chronic mild traumatic brain injury (mTBI)

Inflammatory cytokines have been shown to be elevated following mTBI. Sleep disorders are also commonly reported following mTBI, and are also associated with inflammation in otherwise healthy individuals. Despite the common co-occurrence of inflammatory upregulation and sleep disorders following mTBI, whether these two processes are linked in the chronic stages of injury has not been reported.

Sleep quality scores, peripheral blood samples, and clinical history was collected from 182 warfighters (n=138 mTBI; n=44 controls) during enrollment in the Chronic Effects of Neurotrauma Consortium study. Single molecule array was used to quantify plasma and plasma-derived biomarkers of inflammation (IL-6, IL-10, TNFα cytokines). Spearman’s correlations and linear regression models were used to evaluate relationships between sleep quality and cytokine levels.

Sleep quality was significantly associated with exosomal levels of IL-10 (ß(SE) = 0.11(0.04), p = .01) and TNFα (ß(SE) = 0.07(0.03), p < .01) in the mTBI cohort. mTBI patients who reported clinically significant poor sleep (Pittsburgh Sleep Quality Index ≥ 10) demonstrated significantly elevated exosomal IL-10 compared to those reporting good sleep (ß(SE) = 0.12(0.04), p < .01). Plasma-derived associations were not significant.

Our findings point to a significant association between self-report sleep quality and inflammation in chronic mTBI patients. Clinically, those with a high likelihood of sleep disorders (according to PSQI-defined poor sleep) demonstrate elevated levels of inflammatory cytokines. Signal from exosomes, though smaller in magnitude, may have stronger clinical associations than from plasma. Sleep-focused interventions may also serve to regulate chronic inflammatory processes in these patients. Larger prospective studies are needed to investigate the mechanisms and therapeutic implications of the likely bi-directional relationship between sleep and inflammation following mTBI.