Role of IFN-gamma 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.
Qiu
G
G
Department of Cell Biology, University of Medicine and Dentistry, New Jersey School of Osteopathic Medicine, Stratford 08084, USA.
Wang
C
C
Smith
R
R
Harrison
K
K
Yin
K
K
D000818:Animals; D002429:Cecal Diseases / Q000209:etiology / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D008297:Male; D010529:Peritoneal Cavity / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology*; D000267:Tissue Adhesions / Q000209:etiology / Q000473:pathology
D018932:Chemokine CCL2; D018664:Interleukin-12; D007371:Interferon-gamma