Progesterone inhibits in-vitro embryotoxic Th1 cytokine production to trophoblast in women with recurrent pregnancy loss

A dichotomous T-helper 1 (Th1) versus T-helper 2 (Th2) cytokine response to trophoblast has been proposed to mediate reproductive failure and success, respectively. Progesterone has immunosuppressive properties. In this study, peripheral blood mononuclear cells from women with and without unexplained recurrent pregnancy loss who had and did not have evidence of embryotoxic, Th1 immunity to trophoblast were cultured with progesterone (10(-5) mol/l) or interleukin (IL)-10 (1500 pg/ml) to determine whether these agents were capable of inhibiting embryotoxic, Th1 immunity to trophoblast. The effects of progesterone on Th2 cytokines and transforming growth factor (TGF)-beta secretion were also assessed. Progesterone was found to specifically block Th1 immunity to trophoblast, as was IL-10. Progesterone also appeared to upregulate TGF-beta secretion in response to trophoblast but had no effect on Th2 cytokine secretion. Our data suggest that assaying Th1 cytokines in supernatants of peripheral blood mononuclear cells cultured with a protein extract from trophoblast may identify individuals more likely to benefit from potentially immunosuppressive doses of progesterone. An appropriately designed clinical trial is needed to determine whether therapies modifying Th1 cytokine secretion in response to trophoblast are useful in the clinical management of recurrent pregnancy loss in women producing these cytokines in response to reproductive antigen stimulation.