Interferon-gamma (IFN-gamma) is a specific activator of macrophage function
and plays a critical role in the host immune defense to bacterial infectio
n. In this study we examined the role of IFN-gamma in the regulation of bac
terial load in the cecal ligation and puncture (CLP) model of intra-abdomin
al sepsis in the rat. In initial studies, levels of IL-12, MCP-1, and IFN-g
amma 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 co
mpared to sham controls and this difference was maintained at 48 h after CL
P. Interestingly, IFN-gamma levels were not significantly increased 24 h af
ter CLP, but were increased at 48 h after CLP. These results clearly sugges
t that although an inflammatory response had occurred 24 h post-surgery, wi
th increases in the proinflammatory cytokine IL-12 and the potent chemotact
ic agent MCP-1, levels of IFN-gamma in CLP rats were similar to sham contro
ls. To further investigate the role of IFN-gamma on the development of seps
is we examined the effect(s) of administering anti-IFN-gamma antibody on ba
cterial load after CLP. We show that use of anti-IFN-gamma antibody can sig
nificantly 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.