Early versus late profiles of inflammatory cytokines after mild TBI and their association with neuropsychological outcomes.

Introduction Despite pre-clinical evidence for the role of inflammation in 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. Methods 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 hours 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. Results 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 IL-2 (p=0.014) and IL-6 (p=0.01) within 24 hours post-injury were significantly higher for mTBI patients as compared to OI controls. Elevated plasma IL-2 at 24 hours was associated with more severe one 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). Conclusions Plasma cytokine levels (within 24 hours 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.