Hydroxyprogesterone caproate and progesterone increase tumor necrosis factor-alpha production in lipopolysaccharide stimulated whole blood from non-pregnant women

Objective: Hydroxyprogesterone caproate (17-P) and progesterone have been shown to decrease the rate of preterm birth in high-risk pregnant women, but the mechanism of action is unknown. We hypothesized that 17-P or progesterone would reduce production of the proinflammatory cytokine, tumor necrosis factor-alpha ( TNF-alpha), after lipopolysaccharide (LPS) stimulation of whole blood. Study design: Whole blood collected from 10 non-pregnant women in the follicular phase was treated with LPS ( 1000 ng/mL) alone or with either 17-P or progesterone ( 125 ng/mL and 1250 ng/mL) and LPS. Supernatant collected after 24 h was tested for TNF-alpha by enzyme immunoassay. Results were compared using the Wilcoxon rank sum test. Results: Whole blood treated with 17-P or progesterone in addition to LPS produced significantly higher TNF-alpha concentrations than blood treated with LPS alone. Conclusion: 17-P and progesterone appear to have a pro-inflammatory effect during LPS stimulation of blood from non-pregnant women in vitro. Our data suggest that the reduction in pre-term birth in women treated with progesterone is not mediated through an anti-inflammatory effect on peripheral blood cells.