Effects of adrenocorticotropin and endotoxin on adrenal stimulation and resistance to infection

¹ National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and Walter Reed Army Medical Center, Washington, D. C.

Endotoxin elicited an increase in the urinary excretion of three unconjugated (free) polar corticosteroids in guinea pigs, similar to that observed following adrenocorticotropin (ACTH) administration. The analytical procedure employed ethyl acetate extraction of urine, followed by paper chromatographic separation (chloroform-formamide system) and measurement by the Porter-Sibler method. The larger portion of the increased excretion, following endotoxin, was attributable to the combined 6(ß)-hydroxycortisol and 2()-hydroxycortisol fractions, in comparison to that of cortisol alone. With repeated administration of endotoxin, there were increases in the free polar corticosteroid excretion, less than those observed originally. This decrease was attributed to concurrent stimulation and accumulative impairment of the adrenocorticoid secretory mechanism by endotoxin. Parallel experiments in mice demonstrated no sparing effect of the pretreatment with ACTH upon challenge with viable E. coli, in contrast to the protection afforded by pretreatment with endotoxin.