TNF-related apoptosis-inducing ligand deficiency enhances survival in murine colon ascendens stent peritonitis.

ABSTRACT

BACKGROUND: Apart from inducing apoptosis in tumor cells, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) influences inflammatory reactions. Murine colon ascendens stent peritonitis (CASP) represents a model of diffuse peritonitis. Recently, it has been demonstrated that administration of exogenous TRAIL not only induces apoptosis in neutrophils but also enhances survival in this model. The aim of this study was to examine the impact of genetic TRAIL deficiency on the course of CASP. METHODS: Peritonitis was induced in 6- to 8-week-old female TRAIL (-/-) mice as well as in wild-type mice. The sepsis severity score and survival of mice were monitored. Bacterial loads in blood as well as in the lymphoid organs were examined. Additionally, the number of apoptotic cells within the lymphoid organs was determined. RESULTS: As early as 8 hours postinduction of CASP, TRAIL (-/-) mice were significantly more affected by sepsis than wild-type mice, as measured by the sepsis severity score. However, during the further course of sepsis, TRAIL deficiency led to significantly decreased sepsis severity scores, resulting in an enhanced overall survival in TRAIL (-/-) mice. The better survival of TRAIL (-/-) mice was accompanied by a decreased bacterial load within the blood. In marked contrast, the number of apoptotic cells within the lymphoid organs was highly increased in TRAIL (-/-) mice 20 hours after induction of CASP. CONCLUSION: Hence, exogenous and endogenous TRAIL is protective during the early phase of sepsis, while endogenous TRAIL appears to be detrimental in the later course of this disease.