This laboratory reported that a single subcutaneous (SC) injection of the natural
steroid hormone dehydroepiandrosterone (
DHEA) resulted in significant protection against a lethal herpes virus type 2
encephalitis or a systemic coxsackievirus B4
infection. Our previous results have shown that SC injection of
DHEA resulted in upregulation of the specific host immune response resulting in protection against a lethal
infection. This
hormone did not have any direct
antiviral effects in vitro. Furthermore, results indicate that, in vivo,
DHEA is not the agent directly mediating the upregulation of the immune response. In the skin,
DHEA is converted to
androstenediol (AED) and it, in turn, is converted to androstenetriol; this is a metabolic process which appears unique to the skin. This report demonstrates that SC injection of AED results in markedly greater resistance against both viral and
bacterial infection. Both
DHEA and AED appear to function by facilitating and upregulating host immune responses via mobilization of cutaneous immunity to obtain systemic protection against
infections. Because these
steroids are native to the host and are regulated by the central nervous system, it is suggested that they may be an integral
element of neuroimmunomodulation.