REGULATION OF THE IMMUNE-RESPONSE BY DEHYDROEPIANDROSTERONE AND ITS METABOLITES

Citation
Rm. Loria et al., REGULATION OF THE IMMUNE-RESPONSE BY DEHYDROEPIANDROSTERONE AND ITS METABOLITES, Journal of Endocrinology, 150, 1996, pp. 209-220
Citations number
43
Categorie Soggetti
Endocrynology & Metabolism
Journal title
ISSN journal
00220795
Volume
150
Year of publication
1996
Supplement
S
Pages
209 - 220
Database
ISI
SICI code
0022-0795(1996)150:<209:ROTIBD>2.0.ZU;2-6
Abstract
Dehydroepiandrosterone (5-androsten-3 beta-ol-17-one, DHEA) has been s hown to protect mice from a variety of lethal infections. This include s, but is not limited to, infection with viruses (herpes virus type 2, coxsackie virus B4 (CB4)), bacteria (Enterococcus faecalis, Pseudomon as aeruginosa), and a parasite (Cryptosporidium parvum). We have previ ously reported that androstenediol (5-androstene-3 beta,17 beta-diol, AED), derived from DHEA, is at least 100 x more effective in up-regula ting systemic resistance against CB4 infection than its precursor. Fur thermore, androstenetriol (5-androstene-3 beta,7 beta,17 beta-triol, A ET) which is formed by 7 beta hydroxylation of AED, was more effective against CB4 infection than its precursor, AED. Neither steroid, howev er, has shown any significant direct antiviral effects. The in vitro i nfluences of DHEA, AED and AET on a mitogen-induced mixed splenocyte p roliferation assay were determined. The results showed that DHEA suppr essed the proliferation of concanavalin A (ConA)- or lipopoly-sacchari de-activated cultures in a dose-dependent manner. AED had little influ ence on the activation response. However, AET potentiated the response to both mitogens significantly above the control level. The regulatio n of interleukin (IL)-2 and IL-3 secretion from ConA-activated lymphoc ytes was analogous to these observations. These functions were depress ed by DHEA, unaffected by AED, and potently increased by AET. Moreover , the classic immunosuppressive effects of hydrocortisone on ConA-indu ced lymphocyte proliferation, as well as IL-2 and IL-3 production, wer e unaffected by co-culture with DHEA and only minimally counteracted b y AED. In contrast, AET significantly counteracted the effect of hydro cortisone when co-cultured together. These data show that while DHEA, AED and AET each function in a similar manner in vivo, in vitro their effects are dramatically different from one another with only AET pote ntiating the cellular response by increasing lymphocyte activation and counteracting the immunosuppressive activity of hydrocortisone.