BETHESDA, MD – Occurring immediately after mild traumatic brain injury (mTBI), elevations of inflammatory cytokine levels can persist for years and are associated with neuropsychological outcomes, including depression and PTSD symptoms.
In addition, according to Uniformed Services University of the Health Sciences-led researchers, sleep disorders, another common sequelae of mTBI, are independently associated with inflammation in patients who are otherwise healthy.
“However, whether sleep and inflammation are linked in chronic mTBI has not been reported,” the authors noted.
In response, they conducted a retrospective cross-sectional cohort of warfighters to investigate the hypothesis that inflammation might be linked to sleep quality in chronic mTBI. Results were published in Frontiers of Pharmacology.1
For the study, clinical history, peripheral blood samples, and sleep quality scores were collected from 182 warfighters –138 with mTBI and 44 controls –during enrollment in the Chronic Effects of Neurotrauma Consortium study.
Researchers quantified biomarkers of inflammation (IL-6, IL-10, TNFα cytokines) from plasma and plasma-derived extracellular vesicles (EVs) using single molecule array. They then assessed the relationships between sleep quality and cytokine levels, controlling for age, sex, and BMI.
Clinical cutoff scores for sleep quality were used to divide mTBI patients into “good” and “poor” sleepers, with cytokine levels compared between groups.
Results indicated that, in mTBI participants, sleep quality was significantly associated with EV levels of IL-10 [ß (SE) = 0.11 (0.04), p = 0.01] and TNFα [ß (SE) = 0.07 (0.03), p < 0.01]. “When divided according to “good” versus “poor” sleepers, those reporting poor sleep had significantly elevated EV IL-10 compared to those reporting good sleep [ß (SE) = 0.12 (0.04), p < 0.01],” researchers reported. “Plasma-derived associations were not significant. No associations were found between sleep quality and cytokine levels in controls.”
The authors advised that their results “suggest a significant relationship between sleep quality and chronic inflammation in mTBI patients. Clinically, mTBI patients with a high likelihood of sleep disorders demonstrate elevated levels of inflammatory cytokines. Signal from EVs, 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.”
The study team called for larger prospective studies to investigate the mechanisms and therapeutic implications of the likely bi-directional relationship between sleep and inflammation following mTBI.”
- Gottshall JL, Guedes VA, Pucci JU, Brooks D, et. al. Poor Sleep Quality is Linked to Elevated Extracellular Vesicle-Associated Inflammatory Cytokines in Warfighters With Chronic Mild Traumatic Brain Injuries. Front Pharmacol. 2022 Jan 27;12:762077. doi: 10.3389/fphar.2021.762077. PMID: 35153739; PMCID: PMC8829004.
