Inhibition of gamma interferon decreases bacterial load in peritonitis by accelerating peritoneal fibrin deposition and tissue repair.

Abstract

Bowel perforation can lead to significant bacterial spillage, which may then cause septic peritonitis, characterized by a systemic inflammatory response and organ dysfunction. There are several reports that have shown that the development of peritoneal adhesions is dependent on inflammatory cytokine levels and that these adhesions can reduce bacterial spread, possibly by sealing off the cecum in the cecal ligation and puncture (CLP) model of septic peritonitis. There have not, however, been any studies that have utilized a strategy to accelerate tissue repair in order to seal off the injured cecum and reduce bacterial spread as well as ameliorate systemic inflammation. In the present study, we demonstrate that the administration of anti-gamma interferon (IFN-gamma) antibody (1.2 mg/kg of body weight, intravenously) accelerated tissue repair via increased fibrin deposition 12 and 24 h after CLP in rats. This increase in fibrin deposition was associated with peritoneal adhesion 24 h after CLP and a reduction in bacterial load compared to the bacterial load of rats given irrelevant antibody. Plasma fibrin levels, however, were not altered after IFN-gamma antibody administration, suggesting that the inhibition of IFN-gamma activity specifically increased fibrin deposition to the site of injury. Furthermore, plasma interleukin-6, used as a marker of systemic inflammatory response, was reduced in CLP rats given IFN-gamma antibody compared to that found in those given irrelevant antibody. These results suggest that the early inhibition of IFN-gamma activity in the CLP model is beneficial by accelerating fibrin deposition in cecal tissue to prevent bacterial spread and reduce the systemic inflammatory response. Importantly, increased fibrin deposition in the ceca was not associated with increased plasma fibrin whereas the latter may have detrimental effects associated with coagulation disorders.