Single and Combined Effect of 17ß-Estradiol on Leishmania tropica Killing in Human Macrophages

17β-estradiol (E2), the predominant and most biologically active form of estrogen has been shown to modulate various macrophage activities, sometimes with opposite effects, related to experimental conditions. The aim of this study was to investigate the effect of E2 alone or in combination with PKA inhibitor H-89 or recombinant human chorionic gonadotropin (rhCG) on leishmanicidal activity and cytokines production by human monocytes-derived macrophages infected with Leishmania tropica in vitro. Parasite killing by human monocyte-derived macrophages was microscopically evaluated by Giemsa dye. Nitric oxide release was measured by Griess reaction for nitrites. Whereas, pro-inflammatory cytokines release were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). Results showed that treatment with E2 reduced the percentage of infected cells, as well as the parasite burden per cell. In addition, macrophages treated with E2 prior to L. tropica infection produced more IL-12(p40), IL-6 and nitric oxide (NO) than L. tropica infectedmacrophages. However, these leishmanicidal and immunomodulator activities of E2 on L. tropica-infected macrophages were completely abolished when these cells were treated with E2 in combination with rhCG plus IFNγ. On the other hand, E2-induced phagocytic activity accompanied with cytokines production in L. tropicainfected macrophages greatly increased when the PKA inhibitor H-89 was added to inactivate intracellular PKA signaling pathway. From these data, we conclude that the implication of estrogen in combination with H-89 appears to be an effective strategy to enhance macrophage functions against L. tropica in vitro.