Dehydroepiandrosterone functions as more than an antiglucocorticoid in preserving immunocompetence after thermal injury.
Reduced cellular immune responses and altered cytokine production by cells from mice exposed to thermal injury are minimized if dehydroepiandrosterone (DHEA) is administered after experimental burn injury in mice. An analysis of similar tests of immune function developed by mice given the antiglucocorticoid, 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]17 alpha-propynyl-estra-4,5-diene-3-one (RU486), after the burn revealed no difference in immune function between the RU486-treated mice and the untreated burn group. At the levels of drug used, both DHEA and RU486 were able to completely block the effects of glucocorticoid treatment on immune function in mice, establishing a direct antiglucocorticoid activity of each steroid. Because thermal injury-mediated changes in immunity could be overcome by the administration of DHEA, but not RU486, the data suggest that the elevations in adrenal output of glucocorticoids are not responsible for the alterations in immune function after experimental thermal injury of mice. The results of this study have provided further insight into the mechanism of action of DHEA in this experimental model. The ability of DHEA to preserve immune function in severely thermally injured mice appears to extend beyond an antiglucocorticoid activity.
Paradigm Biosciences, Inc., Salt Lake City, Utah 84109.
B
B
Araneo
R
R
Daynes
D000818:Animals; D002056:Burns / Q000276:immunology* / Q000503:physiopathology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000494:pharmacology* / Q000502:physiology; D003877:Dermatitis, Contact / Q000276:immunology / Q000503:physiopathology; D003907:Dexamethasone / Q000008:administration & dosage; D004343:Drug Implants; D005260:Female; D005938:Glucocorticoids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007121:Immunocompetence / Q000187:drug effects* / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology; D012867:Skin / Q000473:pathology; D013154:Spleen / Q000378:metabolism / Q000503:physiopathology
D016207:Cytokines; D004343:Drug Implants; D005938:Glucocorticoids; D015735:Mifepristone; D003687:Dehydroepiandrosterone; D003907:Dexamethasone