DEHYDROPEPIANDROSTERONE FUNCTIONS AS MORE THAN AN ANTIGLUCOCORTICOID IN PRESERVING IMMUNOCOMPETENCE AFTER THERMAL-INJURY

Reduced cellular immune responses and altered cytokine production by c ells from mice exposed to thermal injury are minimized if dehydroepian drosterone (DHEA) is administered after experimental burn injury in mi ce. An analysis of similar tests of immune function developed by mice given the antiglucocorticoid, 17 beta-hydroxy-11 beta-[4-dimethylamino phenyl]17 alpha-propynyl-estra-4, 5-diene-3-one (RU486), after the bur n revealed no difference in immune function between the RU486-treated mice and the untreated burn group. At the levels of drug used, both DK EA and RU486 were able to completely block the effects of glucocortico id treatment on immune function in mice, establishing a direct antiglu cocorticoid activity of each steroid. Because thermal injury-mediated changes in immunity could be overcome by the administration of DHEA, b ut not RU486, the data suggest that the elevations in adrenal output o f glucocorticoids are not responsible for the alterations in immune fu nction after experimental thermal injury of mice. The results of this study have provided further insight into the mechanism of action of DH EA in this experimental model. The ability of DHEA to preserve immune function in severely thermally injured mice appears to extend beyond a n antiglucocorticoid activity.