Mice given
cycloheximide and 0.2 microgram of
endotoxin simultaneously developed ischaemic bilateral
renal cortical necrosis as part of a fatal syndrome.
Endotoxin given 2 h after
cycloheximide, although fatal, failed to produce
renal cortical necrosis. Investigation suggested that, following
endotoxin challenge in
cycloheximide-treated mice, the occurrence or non-occurrence of bilateral
renal cortical necrosis was determined by the concentration of circulating
glucocorticoids at the time of
endotoxin challenge. Thus, below a certain, as yet undefined,
glucocorticoid concentration,
endotoxin does not cause
renal cortical necrosis in
cycloheximide-treated mice. Inhibition of the fibrinolytic system by epsilonaminocaproic
acid (EACA) indicated that protection against
renal cortical necrosis was directly mediated by increased fibrinolytic activity. Since this increased activity occurred during a period of profound
cycloheximide-mediated inhibition of
protein synthesis, it was postulated that pre-existing
plasminogen activator was released from inhibition, and that this release could only occur when the
glucocorticoid concentration fell below a certain critical value.