title: Steroid therapy can modulate gut barrier function, host defense, and survival in thermally injured mice.
abstract: Prednisone may be immunosuppressive and dehydroepiandrosterone may stimulate the immune response, but their effect on gut-origin sepsis caused by bacterial translocation has not been studied. Balb/c mice were treated orally with prednisone (1 or 10 mg/kg/day) or saline for 4 days before receiving gavage with 10 (10) 14 C-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 subcutaneously for 4 days before bacterial gavage and thermal injury. Some groups in each experiment were observed 10 days for mortality and others were sacrificed 4 hr postburn to measure translocation and survival of translocated 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 and mesenteric lymph nodes and greatly impaired killing of translocated E. coli. In contrast, dehydroepiandrosterone (25 mg/kg) did not affect translocation but significantly improved bacterial killing. Prednisone and dehydroepiandrosterone exert opposite effects during gut-derived sepsis.
authors.affiliation: University of Cincinnati College of Medicine, Department of Surgery Transplantation Division, OH 45262-0558, USA.
authors.forename: L
authors.initials: L
authors.lastname: Gianotti
authors.forename: J W
authors.initials: JW
authors.lastname: Alexander
authors.forename: R
authors.initials: R
authors.lastname: Fukushima
authors.forename: T
authors.initials: T
authors.lastname: Pyles
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D002056:Burns / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000494:pharmacology; D004064:Digestive System / Q000276:immunology* / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology / Q000502:physiology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D018805:Sepsis / Q000382:microbiology
chemical_list: D003687:Dehydroepiandrosterone; D011241:Prednisone