Progesterone suppresses the lipopolysaccharide-induced pro-inflammatory response in primary mononuclear cells isolated from human placental blood

Progesterone is an essential hormone that induces deep immune adaptations favoring pregnancy maintenance. We aimed at evaluating the effects of progesterone on the synthesis of pro- and anti-inflammatory cytokines by mononuclear cells isolated from human placental blood stimulated with lipopolysaccharide, emulating an infection-inflammation environment. Mononuclear cells isolated form human placental blood were obtained from nine women undergoing elective cesarean delivery at term (not in labor), isolated by density gradient sedimentation, cultured and co-stimulated with lipopolysaccharide (500ng/ml) from Escherichia coli in the presence or not of progesterone (0.01, 0.1, or 1.0 mu M) for 24h. Culture supernatants were assayed for pro-inflammatory (IL-1, TNF, IL-6), anti-inflammatory (IL-10) cytokines, chemokines (IL-8, MIP-1) and total MMP-9 by ELISA. In comparison with basal conditions, lipopolysaccharide treatment induced IL-1, TNF, IL-6, IL-8, MIP-1, and MMP-9 synthesis. lipopolysaccharide co-treatment with progesterone significantly decreased the bacterial endotoxin-induced IL-1, TNF-, IL-6, IL-8, and MIP-1 secretion. In contrast, co-treatment with progesterone increased the level of IL-10 secreted to the culture medium. The present results support the concept that progesterone can modulate--partially--the inflammatory response of professional immune cells isolated from placental blood. Therefore, progesterone might be part of the natural compensatory mechanism that limits the cytotoxic effects associated with an intrauterine infection process during gestation.