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.