title: Modification of septic shock in mice by the antiglucocorticoid RU 38486.
abstract: The survival rate in murine septic peritonitis was inversely proportional to the size of the needle used for cecal puncture following ligation below the ileocecal valve. The smaller, 20-gauge needle permitted 20% survival. Only 20% of the animals survived 24 hr after cecal puncture with a 20-gauge needle compared to 90% survival after 5 days if mice had been rendered tolerant to lipopolysaccharide (LPS) prior to the induction of peritonitis. A single intravenous injection of 1 mg RU 38486, concurrent with puncture with a 21-gauge needle, lowered survival to only 15% from the control level of 71%. This same dose of the antiglucocorticoid decreased the survival rate to only 35% from 90% in the tolerant group. Tolerance to the lethal effects of endotoxins, possibly responsible for resistance to septic peritonitis, was also abolished by the antiglucocorticoid. Just 1 mg RU 38486 lowered the survival rate to 5% if it was given with 600 micrograms LPS, which permitted 95% survival in LPS-tolerant mice and 60% survival in normal controls. Whereas both 1 mg RU 38486 and 100 micrograms dexamethasone, given alone, sensitized mice to septic peritonitis (15% and 30% survival, respectively), their combined effects neutralized each other, leading to 80% survival vs. 71% in the control group. Thus receptor-mediated glucocorticoid-dependent mechanisms appear important in the pathogenesis of both endotoxin and septic shock, albeit to varying degrees and in a seemingly contradictory manner.
authors.affiliation: Department of Surgery, Albert Szent-Györgyi Medical University, Szeged, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Lazar
authors.forename: G
authors.initials: G
authors.lastname: Lazar
authors.forename: M K
authors.initials: MK
authors.lastname: Agarwal
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015735:Mifepristone / Q000494:pharmacology*; D010538:Peritonitis / Q000503:physiopathology*; D012772:Shock, Septic / Q000503:physiopathology*
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D015735:Mifepristone; D003907:Dexamethasone