Effects of DHEA (Dehydroepiandrosterone) on Host Virus Interactions

miquelangeles

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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 prior to initiation of infection. 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 protection was most evident when a large inoculum of virus was given, suggesting that the protective mechanism required a triggering action by the virus. DHEA was not effective in genetically immunodeficient HRSJ hrhr mice and did not demonstrate antiviral activity in vitro. While the molecular basis for DHEAs 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 acquired immune deficiency syndrome e.g., HIV deserves intensive study. Keywords Coxsackievirus, Herpesvirus, Immune regulation, Resistance, Infection, HIV, Hematology, Antiviral agents.

We have established that protection against acute lethal viral infections with the native steroid hormone dehydroepiandrosterone (DHEA) is practical.

This protection is achieved not by a direct effect against the infectious agent but apparently by up regulation of the host immune response to combat the infectious process. Our results have shown that:

[1] DHEA at concentrations of 2 - 20 uM failed to influence CVB4 replication in vitro, where immune mechanisms are not present.

[2] DHEA was ineffective in the inbred HRS/J hr/hr mouse which is genetically immunodeficient.

[3] Up-regulation of the immune response by DHEA was seen in CVB4-infected mice - with regard to the number of spleen IgM and IgG AFC, Figure 4 in attached manuscript.

[4] Administration of DHEA alone was also associated with enlargement of the spleen germinal centers which suggests stimulation of the B lymphocyte dependent areas.

[5] DHEA treatment of CVB4-infected animals resulted in a reduction of the "starry sky pattern", an indicator of cell killing, which was prominent in the spleens of CVB4-infected mice not treated with DHEA.

[6] Finally, an increase in circulating mononuclear cells was observed in DHEA treated/CVB4-infected mice which is consistent with the role of these cells in host defense against CVB4 infection as does the DHEA mediated decline in the splenic "starry sky" pattern.

 

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