Dehydroepinadrosterone (DHEA0, a native adrenal steroid hormone, exhibits a marked decline in production with progressive age and its immunologic function is presently unclear. Thus, the pressent study was undertaken to investigate the effects of
exogenously administered DHEA host reesistance to listeria monocytogenes (LM0 infection at the cellular level.
A significant protective effect was demonstrated in murine LM infection when the steroid was supplemented to both untreated and glucocorticosteroid (GCS)-treated mice. To elucidate the possible mechanisms for increased resistance to LM infection,
the
effect of DHEA on the cytokine production of activated splenocytes or macrophages was assessed. The steroid enhanced TNF-αproduction of peritoneal macrophages stimulated in vitro with LPS in contrast to GCS. And its supplementation was effective
in
reversing GCS-induced depression of TNF-αproduction. Activated splenocytes from DHEA-treated animals exhibited a increased capacity to produce IL-2 and IFN-γ, while those from GCS-treated animals showed a reduced capacity of producing IL-2 and
IFN-γ
leaving IL-4 as the major TCGF. Although Ia-negative cells were predominant in the peritoneal resident macrophages, LM infection caused a marked increase in MHC calss II molecule (Ia antigen) expression. In addition, HEA retreatment resulted in
augmented Ia expression on the peritoneal macrophages during LM infection. proliferation of LM within resident peritoneal macrophages was not inhibited by DHEA treatment in vivo.
These findings suggest that the protective effect of DHEA on the host resistance to LM is associated with increased capacities of splenocytes and macrophages in producing cytokines such as IL-2, IFN-γand TNF-α, in addition to increase in Ia
molecule
expression on the macrophages. Because DHEA is a native steroid that has been used clinically with minimal side effects, the usefulness of DHEA in the therapeutic modulation of intracellular bacterial or viral infections including the acquired
immune
deficiency syndrome deserves intensive study.
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