[[alternative]]An in vivo regulatory role of dehydroepiandrosterone in murine TNF-alfa and TGF-beta production

[[abstract]]Dehydroepiandrosterone (DHEA) is a predominant androgen secreted by adrenal cortex. DHEA has been proposed to play an important role in regulating physiological and immunological system in mammals. Our previous report suggested that DHEA caused an enhancement in TNF-alfa and TGF-beta production by both P388D1 cells and peritoneal macrophage under in vitro condition. The specific aim of present study is to investigate whether DHEA have ability to regulate TNF-alfa and TGF-beta production under in vivo condition. Balb/c mice administrated DHEA subcutaneously were sacrificed at 72 hrs after the treatment, then the serum and peritoneal macrophages were collected. The peritoneal macrophages were cultured with LPS for a period of time and the supernatant was then collected. Both TNF-alfa and TGF-b concentration were quantified using ELISA kits. Results suggested that the TNF-alfa secretion by peritoneal macrophages from the mice injected with 50 ug per g body weight and 100 ug per g body weight of DHEA were significantly increased and reached peak 6 hr after incubation. However, the amount of TNF-alfa secretion by macrophages returned to control level when the dose higher than 100 ug per g body weight was given. Result from RT-PCR analysis confirmed the finding that expression of TNF-alfa mRNA was enhanced by in vivo administration of DHEA. By contrast, the serum level of TNF-alfa was not significantly affected by the drug treatment. The TGF-beta secretion by peritoneal macrophages under in vitro culture did not show a significant difference from mice receiving carrier (100 % ethanol). However, the serum level of TGF-beta of mice injected with 100 ug per g body weight of DHEA was significantly lower than the mice received carrier. Dexamethasone is a potent immunosuppressor. Mice injected 1ug per g body weight of dexamethasone showed a significant reduction in TNF-alfa secretion by peritoneal macrophages. However, injection of DHEA together with dexamethasone could overcome the immunosupressive effect of dexamethasone on TNF-alfa secretion. The serum level of TNF-alfa did not show a significant change in dexamethasone treated mice but it showed a significantly increase in the mice received both DHEA and dexamethasone. Mice received dexamethasone showed a significant increase in the serum level of TGF-beta. However, DHEA could not antagonize the augmented effect of dexamethasone on the serum level of TGF-beta. In conclusion, mice injected DHEA potentiated the TNF-alfa production by peritoneal macrophages but decreased the serum level of TGF-beta. Since the effect of DHEA on both TNF-alfa and TGF-beta production might be interfered by other factors under in vivo condition, the effect of DHEA on the serum level of TNF-alfa and the TGF-beta was not significant. In addition, DHEA might be an effective antagonist to overcome the suppressive effect of dexamethasone on TNF-alfa secretion in vivo.