Role of IFN-γ in bacterial containment in a model of intra-abdominal sepsis

Interferon-gamma (IFN-gamma) is a specific activator of macrophage function and plays a critical role in the host immune defense to bacterial infection. In this study we examined the role of IFN-gamma in the regulation of bacterial load in the cecal ligation and puncture (CLP) model of intra-abdominal sepsis in the rat. In initial studies, levels of IL-12, MCP-1, and IFN-gamma were measured in the peritoneal lavage fluid 24 and 48 h after CLP. IL-12 and MCP-1 levels were both significantly increased at 24 h after CLP compared to sham controls and this difference was maintained at 48 h after CLP. Interestingly, IFN-gamma levels were not significantly increased 24 h after CLP, but were increased at 48 h after CLP. These results clearly suggest that although an inflammatory response had occurred 24 h post-surgery, with increases in the proinflammatory cytokine IL-12 and the potent chemotactic agent MCP-1, levels of IFN-gamma in CLP rats were similar to sham controls. To further investigate the role of IFN-gamma on the development of sepsis we examined the effect(s) of administering anti-IFN-gamma antibody on bacterial load after CLP. We show that use of anti-IFN-gamma antibody can significantly decrease bacterial load in the peritoneum. The mechanism of the effect(s) of anti-IFN-gamma is probably by increasing intestinal adhesions to seal the cecum and reduce bacterial movement into the peritoneum.