Further analysis of lethal factors in cycloheximide-treated mice given low doses of bacterial lipopolysaccharide

Endotoxin challenge (0.2 micrograms per mouse) 6 h after a standard dose of cycloheximide was compared with the previously-reported effects of simultaneous injection of cycloheximide and endotoxin. With the submicrogram dose of endotoxin given 6 h after cycloheximide, fatalities occurred without evidence of thrombogenic bilateral renal cortical necrosis which characterized mice dying after the two agents were given together. Anticoagulation with heparin or with ancrod is life-saving, indicating that cycloheximide-treated mice were fatally susceptible to fibrinogen-to-fibrin conversion, and that, in contrast to the situation where cycloheximide and endotoxin are given simultaneously, there was no essential demand for supplementary glycocorticosteroid. A dose of 5.0 micrograms of endotoxin given 6 h after cycloheximide was fatal; again no renal cortical necrosis occurred, but both ancrod and hydrocortisone were essential to ensure survival.