Effect of Exogenous Steroids and Inhibitors of Steroidogenesis on Endotoxin Shock

Summary

Suppression of corticosteroid production by inhibitors effected a tenfold increase in susceptibility of mice to death from endotoxin shock. Amphenone B and metyrapone caused some increase in susceptibility, but if given more than 1 hr before the endotoxin afforded protection to the test animals. Aminoglutethimide exerted a deleterious effect for at least 24 hr. The effect of the aminoglutethimide was reversed by pregnenolone, progesterone and deoxycorticosterone, although the LD₅₀ remained lower than in the control animals. Corticosterone, cortisone and hydrocortisone afforded marked protection in both the endotoxin treated mice as well as the endotoxin-inhibitor treated mice. Andros-tenedione caused a decrease in the LD₅₀ value in both the control and aminoglutethimidetreated mice. By contrast 17-a-hydroxyprogesterone afforded no protection against endotoxin in the control mice and a significant, but miniscule, degree of protection in the inhibitor-treated mice.

This investigation was supported by a U.S. Public Health Service research grant AI-06767, from the National Institute of Allergy and Infectious Diseases.