CONTRIBUTION OF TNF TNF RECEPTOR AND OF FAS LIGAND TO TOXICITY IN MURINE MODELS OF ENDOTOXEMIA AND BACTERIAL PERITONITIS/

Fas/Fas ligand and TNF/TNF receptors are involved in apoptosis. Whethe r both systems are involved in septic shock has not been determined so far We investigated the role of TNF/TNFR and Fas/Fas ligand in models of endotoxemia and of septicemia in mice. Upon LPS challenge TNF and TNFR p55 were involved in the process inducing lethality. Fast did not contribute to enhance lethality, as evidenced in gld mice, lacking Fa sL. Following an intraperitoneal injection of live E. coli, TNF and TN FR p55 were necessary to combat infection. Disruption of either gene w as associated with enhanced lethality and failure to clear the bacteri a. No effect was observed in gld mice in this peritonitis model. Thus, these observations confirmed the pathogenic role of TNF/TNFR in endot oxemia and its beneficial role in local bacterial infections. In addit ion the delta ruled out a major role for Fas/FasL in septic shock in m ice. (C) 1997 Wiley-Liss, Inc.