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

Abstract

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.

Early serum interleukin-8 evaluation may prove useful in localizing abnormally implanted human gestations after in vitro fertilization

“…Human in vitro studies have demonstrated that progesterone stimulates the secretion of T H 2 cytokines (26,27) and inhibits the secretion of T H 1 cytokines (28). Despite differences in serum progesterone levels, we observed no statistically significant difference in IL-2R or IL-6 between groups.…”

RETRACTED: Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial

“…Progesterone might play a significant role in establishing an adequate immune environment at early stages of pregnancy (6,7). The immunological pregnancy-protective effect of progesterone could also be, in part, manifested via controlling cytokine production (8).…”

Women Serum Concentrations of the IL-10 Family of Cytokines and IFN-γ Decrease from the Third Trimester of Pregnancy to Active Labor

“…In fact, it was also demonstrated that, under the effects of progesterone, IL-10 serum levels are elevated, which results in suppression and activation of Th1-and Th2-type cytokines, respectively [32] . It is noteworthy that in vitro the simultaneous activity of progesterone and IL-10 on trophoblasts may be able to suppress proinflammatory responses and to enhance regulated cross talk between the placenta and the decidua [33] .…”