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Infect Immun, May 1998, p. 2300-2309, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Essential Role of Gamma Interferon in Survival of Colon Ascendens Stent Peritonitis, a Novel Murine Model of Abdominal Sepsis

Niko Zantl,1,2 Annette Uebe,1,2 Brigitte Neumann,1 Hermann Wagner,1 Jörg-Rüdiger Siewert,2 Bernhard Holzmann,1,2 Claus-Dieter Heidecke,2 and Klaus Pfeffer1,*

Institute of Medical Microbiology, Immunology and Hygiene1 and Department of Surgery, Klinikum rechts der Isar,2 Technical University of Munich, D-81675 Munich, Germany

Received 15 October 1997/Returned for modification 16 December 1997/Accepted 12 February 1998

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 (IFNgamma R-/-) 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.

* Corresponding author. Mailing address: Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstr. 9, D-81675 Munich, Germany. Phone: 49 89 4140 4132. Fax: 49 89 4140 4139. E-mail: klaus.pfeffer{at}lrz.tu-muenchen.de.

Infect Immun, May 1998, p. 2300-2309, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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