title: Essential role of gamma interferon in survival of colon ascendens stent peritonitis, a novel murine model of abdominal sepsis.
abstract: Despite considerable progress, peritonitis and sepsis remain life-threatening conditions. To improve the understanding of the pathophysiology encountered in sepsis, a new standardized and highly reproducible murine model of abdominal sepsis termed colon ascendens stent peritonitis (CASP) was developed. In CASP, a stent is inserted into the ascending colon, which generates a septic focus. CASP 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 in 38 or 68% mortality, respectively. 14G CASP surgery leads to a rapid invasion of bacteria into the peritoneum and the blood. As a consequence, endotoxemia occurs, inflammatory cells are recruited, and a systemic inflammatory response syndrome develops. Interestingly, the most pronounced upregulation of inflammatory cytokines (gamma interferon [IFN-gamma], tumor necrosis factor alpha [TNF-alpha] and interleukin-12) is observed in spleen and lungs. CASP surgery followed by stent removal at specific time intervals revealed that all animals survived if intervention was performed after 3 h, whereas removal of the septic focus after 9 h did not prevent death, suggesting induction of autonomous mechanisms of a lethal inflammatory response syndrome. 18G CASP surgery in IFN-gamma receptor-deficient (IFNgammaR-/-) mice revealed an essential role of IFN-gamma in survival of sepsis, whereas TNF receptor p55-deficient (TNFRp55-/-) mice did not show altered survival rates. In summary, this study describes a novel animal model that closely mimics human sepsis and appears to be highly suitable for the study of the pathophysiology of abdominal sepsis. Importantly, this model demonstrates a protective role of IFN-gamma in survival of bacterial sepsis.
authors.affiliation: Institute of Medical Microbiology, Immunology and Hygiene and Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Zantl
authors.forename: A
authors.initials: A
authors.lastname: Uebe
authors.forename: B
authors.initials: B
authors.lastname: Neumann
authors.forename: H
authors.initials: H
authors.lastname: Wagner
authors.forename: J R
authors.initials: JR
authors.lastname: Siewert
authors.forename: B
authors.initials: B
authors.lastname: Holzmann
authors.forename: C D
authors.initials: CD
authors.lastname: Heidecke
authors.forename: K
authors.initials: K
authors.lastname: Pfeffer
mesh_terms: D000005:Abdomen / Q000382:microbiology*; D000818:Animals; D003106:Colon; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000209:etiology; D005260:Female; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000401:mortality*; D017471:Receptors, Interferon / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D018805:Sepsis / Q000401:mortality*; D015607:Stents; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D017471:Receptors, Interferon; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor