Androstenediol regulates systemic resistance against lethal infections in mice

We previously reported that subcutaneous injection of DHEA (5-androsten-3 beta-ol-17-one, dehydroepiandrosterone) protected mice from lethal infection. This included both a lethal herpes virus type 2 encephalitis and a lethal systemic coxsackievirus B4 (CB4) infection. Androstenediol (5-androsten-3 beta-17 beta-diol, AED), a metabolic product of DHEA is up to 100 x more effective in regulating systemic resistance against lethal infection with CB 4 than its precursor DHEA. Compared to DHEA, treatment with AED was markedly superior in protecting mice against virus induced myocardiopathy, pancreopathy, and mortality. In addition to its protective effect, AED but not DHEA, induced a 3-4 fold proliferation of the spleen and thymus in virus infected animals; this effect of AED was only seen above a certain threshold dose. Neither steroid, however, has shown any significant direct antiviral effect in vitro; similarly, virus tissues titers in vivo are not affected by the hormones. Additionally, both DHEA and AED protected against a lethal infection with Enterococcus faecalis. These observations demonstrate that the steroid hormones DHEA and AED provide a novel approach for prevention and protection of the host from a variety of infectious diseases.