Early versus Late Profiles of Inflammatory Cytokines after Mild Traumatic Brain Injury and Their Association with Neuropsychological Outcomes.

Despite pre-clinical evidence for the role of inflammation in traumatic brain injury (TBI), there is limited data on inflammatory biomarkers in mild TBI (mTBI). In this study, we describe the profile of plasma inflammatory cytokines and explore associations between these cytokines and neuropsychological outcomes after mTBI. Patients with mTBI with negative computed tomography and orthopedic injury (OI) controls without mTBI were prospectively recruited from emergency rooms at three trauma centers. Plasma inflammatory cytokine levels were measured from venous whole-blood samples that were collected at enrollment (within 24 h of injury) and at 6 months after injury. Neuropsychological tests were performed at 1 week, 1 month, 3 months, and 6 months after the injury. Multivariate regression analysis was performed to identify associations between inflammatory cytokines and neuropsychological outcomes. A total of 53 mTBI and 24 OI controls were included in this study. The majority of patients were male (62.3%), and injured in motor vehicle accidents (37.7%). Plasma interleukin (IL)-2 (p = 0.01) and IL-6 (p = 0.01) within 24 h post-injury were significantly higher for mTBI patients compared with OI controls. Elevated plasma IL-2 at 24 h was associated with more severe 1-week post-concussive symptoms (p = 0.001). At 6 months, elevated plasma IL-10 was associated with greater depression scores (p = 0.004) and more severe post-traumatic stress disorder (PTSD) symptoms (p = 0.001). Plasma cytokine levels (within 24 h and at 6 months post-injury) were significantly associated with early and late post-concussive symptoms, PTSD, and depression scores after mTBI. These results highlight the potential role of inflammation in the pathophysiology of post-traumatic symptoms after mTBI.