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.
Institute of Medical Microbiology,
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-
], tumor necrosis factor alpha
[TNF-
] 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-
receptor-deficient (IFN
R
/
) mice revealed an
essential role of IFN-
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-
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.
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