Labor-associated changes in interleukin-10 production and its regulation by immunomodulators in human choriodecidua

KL Simpson, Jeffrey Keelan, MD Mitchell

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    Abstract

    Parturition is associated with increased production of proinflammatory mediators by gestational tissues. Interleukin-10 (IL-10) is an antiinflammatory cytokine produced by human chorion, decidual, and trophoblast tissues. To study the effects of immunomodulators on IL-10, IL-6, and PGE(2) production by human choriodecidua before and after labor, an organ explant system was established. Tissue disks (6 mm) were excised from choriodecidual membranes obtained at term by cesarean section before labor (n = 6-7) or after spontaneous vaginal delivery (n = 7-8). After 24-h equilibration in medium, the tissues were treated with IL-1 beta (10 ng/mL), tumor necrosis factor-tu (100 ng/mL), Lipopolysaccharide (5 mu g/mL), dexamethasone (1 mu mol/L), or an appropriate vehicle control (n = 8 wells/treatment) for 24 h. Media were harvested, and IL-10, IL-6, and PGE(2) concentrations were determined by immunoassay. Basal choriodecidual production rates of IL-10 mere significantly decreased with labor (P <0.001), whereas PGE(2) and IL-6 production rates increased. The production of all three substances was increased by IL-1 beta, tumor necrosis factor-alpha, and lipopolysaccharide, but inhibited by dexamethasone. In contrast to PGE(2) and IL-6, there was significantly increased responsiveness of IL-10 production to inflammatory stimuli after labor, but decreased responsiveness to the inhibitory effects of dexamethasone. These data indicate that IL-10 could play a role in modulating or promoting resolution of the inflammatory processes associated with labor at term and with intrauterine infection-associated preterm labor. Media were harvested, and IL-10, IL-6, and PGE(2) concentrations were determined by immunoassay. Basal choriodecidual production rates of IL-10 mere significantly decreased with labor (P <0.001), whereas PGE(2) and IL-6 production rates increased. The production of all three substances was increased by IL-1 beta, tumor necrosis factor-alpha, and lipopolysaccharide, but inhibited by dexamethasone. In contrast to PGE(2) and IL-6, there was significantly increased responsiveness of IL-10 production to inflammatory stimuli after labor, but decreased responsiveness to the inhibitory effects of dexamethasone. These data indicate that IL-10 could play a role in modulating or promoting resolution of the inflammatory processes associated with labor at term and with intrauterine infection-associated preterm labor.
    Original languageEnglish
    Pages (from-to)4332-4337
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume83
    DOIs
    Publication statusPublished - 1998

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