Natural adrenocorticosteroids do not restore resistance to endotoxin in the adrenalectomized mouse

Chronic loss of adrenocorticosteroid activity by adrenalectomy (10 days) or acute inhibition of glucocorticoid receptor function by injection of an anti-progestin (RU-38486) increased sensitivity to lipopolysaccharide about 200-fold, compared to that of control animals. Daily subcutaneous injection of a mixture of the natural glucocorticoid corticosterone and the mineralocorticoid deoxycorticosterone did not restore resistance to the endotoxin. The largest dose of steroid, 400 micrograms corticosterone + 200 micrograms deoxycorticosterone, provided only partial protection against 20 micrograms LPS, which was 10% of the LD50 for animals with adrenals. The mechanisms involved in lack of effectiveness of natural corticosteroids will require further experimentation.