In vitro potentiation of lymphocyte activation by dehydroepiandrosterone, androstenediol, and androstenetriol.
Dehydroepiandrosterone (5-androstene-3 beta-ol-17-one, DHEA) has been shown to protect mice from lethal viral and bacterial infections. However, recently, androstenediol (5-androstene-3 beta-17 beta-diol, AED) and androstenetriol (5-androstene-3 beta-7 beta-triol, AET), metabolites of DHEA, have each shown to be more potent endocrine regulators of the immune response. In contrast to glucocorticosteroids, in vivo, these steroid hormones up-regulated the cellular immune response of the host to limit virus-mediated pathology. These experiments first examined the in vitro influences of DHEA, and AED, or AET on mitogen-stimulated activation of murine lymphocytes. From physiologic to pharmacologic doses, DHEA suppressed proliferation of mixed splenocyte cultures activated with Con A or LPS by 20 to 70% whereas AED had little influence on the response. In sharp contrast, AET potentiated the response with both mitogens to 50 to 70% above control. Analogous to these observations was the regulation of IL-2 and IL-3 secretion from Con A-activated lymphocytes by each of these hormones which again was depressed analyzed. The suppressive effects of hydrocortisone on Con A-induced lymphocyte proliferation and cytokine production were strongly counteracted by coculture with AET. DHEA did not counteract hydrocortisone activity whereas AED showed moderate antiglucocorticoid function.
Padgett
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DA
Department of Microbiology, Immunology, and Pathology, Virginia Commonwealth University's Medical College of Virginia, Richmond 23298.
Loria
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RM
D000734:Androstenediols / Q000494:pharmacology*; D000737:Androstenols / Q000494:pharmacology*; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology
D000734:Androstenediols; D000737:Androstenols; D007376:Interleukin-2; D007377:Interleukin-3; D008070:Lipopolysaccharides; D003208:Concanavalin A; D003687:Dehydroepiandrosterone; D006854:Hydrocortisone