Elevated expression of cyclooxygenase-2 contributes to immune dysfunction in a murine model of trauma

Background. Cyclooxygenase-2 (Cox-2), the inducible form of Cox, is a rate-limiting enzyme in the synthesis of prostaglandins (PGs). Prostaglandin E₂ (PGE₂) and other eicosanoids possess immunosuppressive properties. Previously, traumatic injury was found to stimulate the synthesis of PGs and cause immune dysfunction. In this study a murine model was used to determine the effect of trauma on the expression of Cox-2 in macrophages and to elucidate the role of Cox-2 in trauma-induced immune dysfunction. Methods. Mice were randomized to control or trauma (femur fracture plus 40% blood volume hemorrhage) groups. One, 4, and 7 days after injury, splenic macrophages were isolated and assayed for expression of Cox-2 and production of PGE₂. In addition, the effect of pharmacologically inhibiting Cox-2 or knocking out the Cox-2 gene on trauma-induced suppression of splenocyte mitogenesis was determined. Results. Trauma led to increased expression of Cox-2, enhanced synthesis of PGE₂, and suppressed splenocyte mitogenesis. Both pharmacologic inhibition and genetic deletion of Cox-2 abrogated trauma-mediated suppression of splenocyte mitogenesis. Conclusions. These experiments link trauma-induced increases in Cox-2 expression and PGE₂ production to reduced immune function. Cox-2 represents a potential pharmacologic target to prevent or reverse trauma-induced immunosuppression.