The Centers for Disease Control and Prevention (CDC) have estimated that nearly 2 million people sustain a traumatic brain injury (TBI) annually in the United States. Of these cases, over 300,000 patients require in-patient hospitalization and over 50,000 people die. In fact, TBI is a contributing factor to over 30% of all injury related deaths in the United States. The leading cause of death after TBI is infection and its resultant multisystem organ failure. Several studies have demonstrated that TBI results in a rapid and profound immune suppression. The proposed mechanism by which TBI leaves patients susceptible to secondary infection involves a brain-mediated switch towards an overall anti-inflammatory state. Previous studies have shown that preventing this switch towards an anti-inflammatory state may be a novel approach to treating a myriad of infection related problems after injury. The guiding hypothesis of my laboratory is that preventing the TBI-induced anti-inflammatory response will improve survival from secondary infection after TBI. Thus, therapies targeted toward preventing an anti-inflammatory response to brain injury may emerge as a novel tool to combat this highly lethal disorder.