Evidence of an immunosuppressive effect of progesterone upon in vitro secretion of proinflammatory and prodegradative factors in a model of choriodecidual infection.

Abstract

To evaluate whether progesterone (P4) is able to modulate the secretion of tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, IL-10 and matrix metalloproteinase-9 (MMP-9) after choriodecidual stimulation with lipopolysaccharide (LPS). Chorioamnionitis-elicited preterm delivery is associated with an uncontrolled secretion of proinflammatory cytokines that may induce MMPs, which modify the fine immunological and structural equilibrium at the fetal-maternal interface. Instituto Nacional de Perinatología 'Isidro Espinosa de los Reyes', Mexico City. Twelve human fetal membranes at term from healthy patients were placed in a two-chamber culture system. Choriodecidual and amniotic regions were preincubated with 1.0, 0.1, or 0.01 μmol/l P4 for 24 hours; after which the choriodecidual region was costimulated with 1000 ng/ml of LPS for 24 hours. Descriptive statistics were obtained for each variable. Data distribution was tested for normality using Kolmogorov-Smirnoff and Shapiro-Wilk tests. When distribution was normal, Student's t test was used to analyse for differences among groups. Mann-Whitney's U test was used when data were not normally distributed. Pretreatment with 1.0 μmol/l P4 significantly blunted the secretion of TNF-α, IL-1β, IL-6, IL-8 and IL-10. MMP-9 was inhibited with 0.1 μmol/l P4. Mifepristone (RU486) blocked the immunosuppressive effect of P4, suggesting a P4 effect mediated by its receptor. These results offer evidence to support the concept that P4 can protect the fetal-placental unit through a compensatory mechanism that partially limits the secretion of proinflammatory and prodegradative modulators.