Protection against acute lethal viral infections with the native steroid dehydroepiandrosterone (DHEA)

Abstract

A significant protective effect of a native adrenal steroid, dehydroepiandrosterone (DHEA), was demonstrated in studies of two lethal viral infection models in mice: systemic coxsackievirus B4 and herpes simplex type 2 encephalitis. The steroid was active either by long-term feeding or by a single subcutaneous injection. A closely related steroid, etiocholanolone, was not protective in these models. Histopathological analysis, leukocyte counts, and numbers of spleen antibody forming cells in the coxsackievirus B4 model suggests that DHEA functions by maintaining or potentiating the immune competence of mice otherwise depressed by viral infection. DHEA was not effective in genetically immunodeficient HRS/J hr/hr mice and did not demonstrate antiviral activity in vitro. While the molecular basis for DHEA's effect on the immune system is not known, studies by others suggest that it may counteract the stress related immunosuppressive effects of glucocorticoids stimulated by viral infection. Because DHEA is a native steroid that has been used clinically with minimal side effects, the utility of DHEA in the therapeutic modulation of acute and chronic viral infections including the acquired immune deficiency syndrome deserves intensive study.

16alpha-bromoepiandrosterone, a dehydroepiandrosterone (DHEA) analogue, inhibits Plasmodium falciparum and Plasmodium berghei growth.

“…Exogenous administration of DHEA has been reported to decrease mortality in mice with systemic coxsackievirus B4 infection and with herpes simplex type 2 encephalitis. 15 Decreased DHEA levels have been inversely correlated with progression of disease in HIV and human Tcell lymphotropic virus type I (HTLV-1) infections. 2,3,16 Furthermore, decreased DHEA levels in the elderly have been implicated, at least in part, in age-related immunosenescence.…”

High interleukin-10 production is associated with low antibody response to influenza vaccination in the elderly

“…We previously demonstrated in vitro and in vivo that DHEA can restore the age-related, defective TNF-␣ production in macrophages and mitogen-induced splenocyte proliferation [12]. May et al [23] demonstrated that DHEA administration reversed corticosteroid and stress-induced inhibition of immune function, Loria et al [24] showed that DHEA administration has a protective effect against systemic Coxsackie virus and Herpes simplex type 2 encephalitis, and Daynes et al [25] found that it can enhance IL-2 production by activated murine T cells. In a limited clinical trial, it has been demonstrated that orally administered DHEA (50 mg/daily) to elderly men with low-serum DHEA safely activated several immune functions within 2-20 weeks of treatment, including B and T cell mitogenic response and PHA-induced IL-2 production, suggesting potential therapeutic benefits of DHEA supplementation in immunodeficient states [26].…”

Affectionate Communication Received from Spouses Predicts Stress Hormone Levels in Healthy Adults

“…DHEA-S is more frequently studied in social science research because it has a longer half-life than DHEA and an absence of diurnal variation (Rosenfeld, Rosenberg, Fukushima, & Hellman, 1975). DHEA and DHEA-S appear to have protective functions against a variety of conditions, including HIV (Loria, Inge, Cook, Szakal, & Regelson, 1988), Cushing's disease (Yamaji, Ishibashi, Sekihara, Itabashi, & Yanaihara, 1984), Alzheimer's disease Affectionate Communication 8 (Näsman et al, 1995), and some forms of cancer (Gordon, Helzlsouer, & Comstock, 1991).…”