ENZYME INDUCTION AND CORTISONE PROTECTION IN ENDOTOXIN-POISONED MICE AT 25 C COMPARED WITH THAT AT 5 C

Abstract

Abstract : Mice housed at 25 deg C are protected by cortisone against endotoxin lethality when the hormone is given at the same time as the poison, but not an hour or two later. This is not true of mice housed at 5 deg C. Activity of liver tryptophan pyrrolase is lowered by endotoxin and elevated by cortisone only in animals at normal temperatures. When endotoxin and hormone are given concurrently, normal enzyme activity is maintained, but activity decreases when the hormone injection is given an hour or more after endotoxin. Actinomycin D, ethionine, 2-thiouracil, and 8-azaguanine (inhibitors of protein synthesis) when given in sublethal amount: potentiate endotoxin, prevent cortisone protection against endotoxin, and block the hormonal induction of tryptophan pyrrolase. Chloramphenicol has none of these effects. Mice infected with Salmonella typhimurium have lower than normal tryptophan pyrrolase activity and a smaller induction of enzyme by cortisone 18 hours postinfection than do normal mice or mice 42 hours postinfection. This occurs only at 25 deg C.