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

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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 ofthe pathophysiology encountered in sepsis, a new standardizedand highly reproducible murine model of abdominal sepsis termedcolon ascendens stent peritonitis (CASP) was developed. In CASP,a stent is inserted into the ascending colon, which generatesa septic focus. CASP employing a stent of 14-gauge diameter (14Gstent) results in a mortality of 100% within 18 to 48 h aftersurgery. By inserting stents of small diameters, mortality canbe exactly controlled. Thus, CASP surgery with insertion of a22G or 18G stent (22G or 18G CASP surgery) results in 38 or 68%mortality, respectively. 14G CASP surgery leads to a rapid invasionof bacteria into the peritoneum and the blood. As a consequence,endotoxemia occurs, inflammatory cells are recruited, and a systemicinflammatory response syndrome develops. Interestingly, the mostpronounced 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 stentremoval at specific time intervals revealed that all animals survivedif intervention was performed after 3 h, whereas removal of theseptic focus after 9 h did not prevent death, suggesting inductionof autonomous mechanisms of a lethal inflammatory response syndrome.18G CASP surgery in IFN- $gamma$ receptor-deficient (IFN $gamma$ 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 studydescribes a novel animal model that closely mimics human sepsisand appears to be highly suitable for the study of the pathophysiologyof abdominal sepsis. Importantly, this model demonstrates a protectiverole of IFN- $gamma$ in survival of bacterial sepsis.

^* Corresponding author. Mailing address: Institute of Medical Microbiology, Immunology and Hygiene, Technical University ofMunich, Trogerstr. 9, D-81675 Munich, Germany. Phone: 49 89 41404132. 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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