In vitro effects of genistein and resveratrol on the production of interferon-gamma (IFNgamma) and interleukin-10 (IL-10) by stimulated murine splenocytes.

Phytoestrogens are a group of plant-derived biologically active substances with a chemical structure that resembles that of 17beta-estradiol (E2). As the presence of estrogen receptors (ER) has been identified in several immune cells, phytoestrogens may also have a great impact on the immune system. The aim of our study was to determine the in vitro effects of genistein and resveratrol on the production of interferon-gamma (IFNgamma) and interleukin-10 (IL-10) by stimulated murine splenocytes and compare them with the effects of natural E2. Phorbol 12-miristate 13-acetate (PMA) together with ionomycin was used to stimulate the cells. E2 and genistein did not show any significant effects on the stimulated production of IFNgamma. Resveratrol had a mild inhibitory effect on IFNgamma production at the concentration of 10(-7)M; however, this difference did not reach statistical significance (p>0.05). IL-10 levels in the splenocytes culture supernatants were found to be increased in the presence of E2, genistein and resveratrol; however, these effects were also not statistically significant. To determine whether the exposure to our studied phytoestrogens induced a shift in the T-helper 1/T-helper 2 (Th1/Th2) balance, we calculated the ratio between the production of IFNgamma, the prototypic Th1 cytokine, and the production of IL-10, the prototypic Th2 cytokine, at different concentrations of our tested substances. Genistein at the concentrations of 10(-6) and 10(-7)M and resveratrol at the concentrations of 10(-6)M decreased significantly the IFNgamma/IL-10 ratio. This decrease was comparable to that of E2 at the concentrations of 10(-7)M. From our in vitro experiments we conclude that genistein and resveratrol, similarly to E2, by decreasing the IFNgamma/IL10 ratio may shift the Th1/Th2 balance towards the Th2 response.