[[abstract]]英文摘要 DHEA is a predominant androgen secreted by the adrenal cortex zona reticularis. DHEA appears as an intermediate of the androgen biosynthesis pathway and play a multifunctional role in regulating physiological system in mammals. The accumulated documents have demonstrated that DHEA and DHEAS are the potential immunomodulator that regulate both humoral and cellular immune response. Previous reports showed that DHEA and DHEAS were able to enhance the immunoglobulin production by murine spleen B lymphocytes、human peripheral blood mononuclear cells (PMNC) and B-cell lymphoid cell lines (Dakiki and SKW6.4) under in vitro condition. The present study extended the previous finding to in vivo system. In this study, the male Balb/c mice were injected subcutaneously with various doses of DHEA or DHEAS based on the body weight. The mice were then sacrified at different time point after the drug treatment and both spleen lymphocytes and serum were collected. Results indicated that both the growth rate and viability of the spleen lymphocytes were reduced after 6 days of in vitro culture. However, the amounts of immunoglobulin (IgG、IgA and IgM) secreted by the cells and the serum level of immunoglobulin were increased. The optimal dose for enhancing immuno-globulin secretion was 250 mg per gram body weight and the period for the maximal effect was 48 hrs after the treatment. The previous reports suggested that cytokine including interleukin-10 (IL-10) were able to modulate the immuno-globulin production. In this study, the role of IL-10 in DHEA/DHEAS-mediated increase in immunoglobilin production was investigated. Results indicated that both DHEA and DHEAS were able to enhance the production of IL-10 by the conA-stimulated murine spleen cells. This regulatory activity of DHEA and DHEAS appeared on the messenger RNA level. To further confirm the role of IL-10, the mice were injected with both DHEA and an anti-mouse IL-10 mAb simultaneously. Result showed that the amount of IL-10 produced by the spleen cells was reduced and the serum level of IL-10 was decreased after the antibody treatment. In consistent with the IL-10 level, the amount of immunoglobulin secreted by spleen cells and the serum level of the immunoglobulin were significantly decreased. In conclusion, DHEA might enhance the immunoglobulin production by activing Th2 pathway and increasing IL-10 production.
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