P4 inhibited LPS-induced TLR-4/MyD88 and pro-inflammatory factors in the human amniotic epithelium. These results could explain partially how P4 can protect the amniotic region of fetal membranes and generate a compensatory mechanism that limits the secretion of pro-inflammatory modulators, which could jeopardize the immune privilege during pregnancy.
Synthesis and secretion of IL-10 in response to three different pathogens associated with intrauterine infection and preterm birth are differential and depend on the nature of the microorganism and initial contact region.
Objective
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).
Design
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.
Setting
Instituto Nacional de Perinatología ‘Isidro Espinosa de los Reyes’, Mexico City.
Sample
Twelve human fetal membranes at term from healthy patients were placed in a two‐chamber culture system.
Methods
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.
Main outcome measures
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.
Results
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.
Conclusion
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.
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