Immunomodulation with progestogens as a therapeutic approach in pregnancy complications

Abstract

Pregnancy is confronted with several challenges such as threatened abortion, spontaneous miscarriage, preeclampsia and preterm delivery. Immunologic effectors have been implicated as contributing to the etiopathogenesis of some of these pregnancy complications. Pro-inflammatory and anti-inflammatory cytokines have been investigated for their effects on the conceptus and pregnancy because of their wide-ranging and potent effects on cells and tissues. This review addresses the nexus between pro-inflammatory cytokines and recurrent miscarriage, which is an important complication of pregnancy. It summarizes the possible mechanisms of action of pro-inflammatory cytokines in pregnancy loss, and then proceeds to discuss immunomodulation of cytokine profiles to a state that is favourable to the success of pregnancy. Fascinating leads for possible redirection of cytokine profiles have come from observations on the immunomodulatory capabilities of progesterone. This review presents studies that show that progesterone and the orally-administered progestogen dydrogesterone inhibit pro-inflammatory cytokines and upregulate anti-inflammatory cytokines; it also summarizes clinical studies on progestogen supplementation. These studies lend credibility to the proposal that progestogens should be explored for the immunotherapeutic management of pregnancy complications.