Tumor necrosis factor-dependent adhesions as a major protective mechanism early in septic peritonitis in mice

occurrence of peritoneal adhesions in surgical patients is positively corre lated with tumor necrosis factor (TNF) levels, In a model of septic periton itis-cecal ligation and puncture-TNF neutralization prevented formation of peritoneal adhesions and increased mortality, most likely because localizat ion of the septic focus was prevented. To discriminate between the coagulat ion-independent protective TNF effect and a potential protective procoagula nt TNF effect, formation of peritoneal adhesions after CLP was inhibited wi th heparin, hirudin, or urokinase, Each treatment increased mortality and i ncreased the number of bacteria in the peritoneal lavage fluid, kidney, and liver to various degrees. Under these experimental conditions, antibiotics prevented death. In coagulation-compromised mice, lethality was further en hanced by additional TNF neutralization These findings demonstrate that per itoneal adhesions early in septic peritonitis are an important mechanism of innate immunity that prevents increased spread of bacteria and reduces mor tality.