NATURAL ADRENOCORTICOSTEROIDS DO NOT RESTORE RESISTANCE TO ENDOTOXIN IN THE ADRENALECTOMIZED MOUSE

Chronic loss of adrenocorticosteroid activity by adrenalectomy (10 day s) or acute inhibition of glucocorticoid receptor function by injectio n of an anti-progestin (RU-38486) increased sensitivity to lipopolysac charide about 200-fold, compared to that of control animals. Daily sub cutaneous injection of a mixture of the natural glucocorticoid cortico sterone and the mineralocorticoid deoxycorticosterone did not restore resistance to the endotoxin. The largest dose of steroid, 400 mug cort icosterone + 200 mug deoxycorticosterone, provided only partial protec tion against 20 mug LPS, which was 10% of the LD50 for animals with ad renals. The mechanisms involved in lack of effectiveness of natural co rticosteroids will require further experimentation. (C) 1993 Wiley-Lis s, Inc.