Abstract
BackgroundDuring human pregnancy, infection/inflammation represents an important factor that increases the risk of developing preterm labor. The purpose of this study was to determine if pre-treatment with progesterone has an immunomodulatory effect on human placenta production of endotoxin-induced inflammation and degradation of extracellular matrix markers.MethodsPlacentas were obtained under sterile conditions from pregnancies delivered at term before the onset of labor by cesarean section. Explants from central cotyledons of 10 human placentas were pre-treated with different concentrations of progesterone (0.01, 01, 1.0 μM) and then stimulated with 1000 ng/mL of LPS of Escherichia coli. Cytokines TNFα, IL-1β, IL-6, IL-8, MIP-1α, IL-10 concentrations in the culture medium were then measured by specific ELISA. Secretion profile of MMP-9 was evaluated by ELISA and zymogram. Statistical differences were determined by one-way ANOVA followed by the appropriate ad hoc test; P < 0.05 was considered statistically significant.ResultsIn comparison to the explants incubated with vehicle, the LPS treatment led to a significant increase in the level of all cytokines. In comparison to the explants treated only with LPS, pre-treatment with 0.01–1.0 μM progesterone significantly blunted (73, 56, 56, 75, 25, 48 %) the secretion of TNF-α, IL-1β, IL-6, IL-8, MIP-1α, IL-10, respectively. The MMP-9 induced by LPS treatment was inhibited only with the highest concentration of progesterone. Mifepristone (RU486) blocked the immunosuppressive effect of progesterone.ConclusionsThe present results support the concept that progesterone could be part of the compensatory mechanism that limits the inflammation-induced cytotoxic effects associated with an infection process during gestation.
Highlights
IntroductionInfection/inflammation represents an important factor that increases the risk of developing preterm labor
During human pregnancy, infection/inflammation represents an important factor that increases the risk of developing preterm labor
Taking into account the results obtained from the time-course curve, the LPS-induced cytokines secretion was maximal at 24 h after stimulation
Summary
Infection/inflammation represents an important factor that increases the risk of developing preterm labor. There is evidence that almost 30 % of women with preterm labor have microbial invasion or inflammation of the amniotic cavity [1, 2]; this condition induces uncontrolled production and increase of Th1 cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)α, and IL-6 that alter the intra-amniotic milieu, leading to disruption of fetal tolerance [3]. Evidence supports the existence of a strong relation between the microorganisms that reach the amniotic cavity from the vagina and bacteria identified in the fetal circulation of premature neonates [4]. In this adverse scenario, the placenta represents a physical barrier that protects the product. The placenta allows for the diffusion of nutrients and oxygen from the maternal blood to the fetal blood; this tissue is key in the immune-endocrine relationship between mother and fetus, creating an immune tolerance that permits their co-existence along 40 weeks
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
