ESSENTIAL ROLE OF GAMMA-INTERFERON IN SURVIVAL OF COLON ASCENDENS STENT PERITONITIS, A NOVEL MURINE MODEL OF ABDOMINAL SEPSIS

Despite considerable progress, peritonitis and sepsis remain life-thre atening conditions. To improve the understanding of the pathophysiolog y encountered in sepsis, a new standardized and highly reproducible mu rine model of abdominal sepsis termed colon ascendens stent peritoniti s (CASP) was developed. In GASP, a stent is inserted into the ascendin g colon, which generates a septic focus. GASP employing a stent of 14- gauge diameter (14G stent) results in a mortality of 100% within 18 to 48 h after surgery. By inserting stents of small diameters, mortality can be exactly controlled, Thus, CASP surgery with insertion of a 22G or 18G stent (22G or 18G CASP surgery) results ire 38 or 68% mortalit y, respectively, 14G GASP surgery leads to a rapid invasion of bacteri a into the peritoneum and the blood. as a consequence, endotoxemia occ urs, inflammatory cells are recruited, and a systemic inflammatory res ponse syndrome develops. Interestingly, the most pronounced upregulati on of inflammatory cytokines (gamma interferon [IFN-gamma], tumor necr osis factor alpha [TNF-alpha] and interleukin-12) is observed in splee n and lungs, GASP surgery followed by stent removal at specific time i ntervals revealed that all animals survived if intervention was perfor med after 3 h, whereas removal of the septic focus after 9 h did not p revent death, suggesting induction of autonomous mechanisms of a letha l inflammatory response syndrome, 18G CASP surgery in IFN-gamma recept or-deficient (IFN gamma R-/-) mice revealed an essential role of IFN-g amma in survival of sepsis, whereas TNF receptor p55-deficient (TNFRp5 5(-/-)) mice did not show altered survival rates. In summary, this stu dy describes a novel animal model that closely mimics human sepsis and appears to be highly suitable for the study; of the pathophysiology o f abdominal sepsis. Importantly, this model demonstrates a protective role of IFN-gamma in survival of bacterial sepsis.