STEROID-THERAPY CAN MODULATE GUT BARRIER FUNCTION, HOST-DEFENSE, AND SURVIVAL IN THERMALLY INJURED MICE

Prednisone may be immunosuppressive and dehydroepiandrosterone may sti mulate the immune response, but their effect on gut origin sepsis caus ed by bacterial translocation has not been studied. Balb/c mice were t reated orally with prednisone (1 or 10 mg/kg/day) or saline for 4 days before receiving gavage with 10(10) C-14-labeled Escherichia coli and a 20% thermal injury. Mice were transfused with allogeneic blood and given dehydroepiandrosterone (5 or 25 mg/kg/day) or vehicle subcutaneo usly for 4 days before bacterial gavage and thermal injury. Some group s in each experiment were observed 10 days for mortality and others we re sacrificed 4 hi postburn to measure translocation and survival of t ranslocated bacteria, Survival in prednisone treated animals was 25% ( 10 mg/kg/day) and 75% (1 mg/kg/day) versus 80% for controls. Following dehydroepiandrosterone administration, survival was 72% (25 mg/kg/day /group) and 30% (5 mg/kg/day/group) versus 16% for controls. High dose prednisone increased bacterial translocation to the intestinal wall a nd mesenteric lymph nodes and greatly impaired killing of translocated E. coli. In contrast, dehydroepiandrosterone (25 mg/kg) did not affec t translocation but significantly improved bacterial killing. Predniso ne and dehydroepiandrosterone exert opposite effects during gut-derive d sepsis. (C) 1996 Academic Press, Inc.