Multiple roles for IL-12 in a model of acute septic peritonitis

The present study addressed the role of IL-12 in a murine model of septic p eritonitis, induced by cecal Ligation and puncture (CLP), Although CLP surg ery induced IL-12 production at 6 and 24 h after surgery, IL-12 immunoneutr alization was clearly deleterious in this model: 54% of CLP mice receiving preimmune serum survived, whereas mice administered IL-12 antisera prior to CLP experienced a 25% survival rate, IL-12 immunoneutralization not only l ed to increased mortality, but also appeared to promote a shift away from I L-12 and IFN-gamma, in favor of IL-IO, This cytokine shift corresponded to changes in bacterial load, as CLP mice receiving IL-12 antiserum yielded mo re CFUs from the peritoneal cavity at 24 h after CLP, To address the role o f bacterial infection in IL-12 antiserum-induced mortality following CLP, a ntibiotics were administered for 4 days after surgery. Despite regular anti biotic administration, IL-12 immunoneutralization still reduced survival in CLP mice, Furthermore, histology of the ceca revealed that mice administer ed IL-12 antisera failed to show typical organization of the damaged cecum wall. Accordingly, Gram staining revealed bacteria within peritoneal fluids from these mice, while peritoneal fluids from CLP mice that received preim mune serum and antibiotics were free of bacteria. Altogether, these data su ggested multiple important roles for IL-12 in the evolution of murine septi c peritonitis.