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Labor-Associated Changes in Interleukin-10 Production and Its Regulation by Immunomodulators in Human Choriodecidua

Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, Private Bag, 92109 Auckland, New Zealand

Address all correspondence and requests for reprints to: Dr. J. A. Keelan, Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, Private Bag, 92109 Auckland, New Zealand. E-mail: j.keelan{at}auckland.ac.nz

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 PGE₂ 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-1ß (10 ng/mL), tumor necrosis factor- (100 ng/mL), lipopolysaccharide (5 µg/mL), dexamethasone (1 µmol/L), or an appropriate vehicle control (n = 3 wells/treatment) for 24 h. Media were harvested, and IL-10, IL-6, and PGE₂ concentrations were determined by immunoassay. Basal choriodecidual production rates of IL-10 were significantly decreased with labor (P < 0.001), whereas PGE₂ and IL-6 production rates increased. The production of all three substances was increased by IL-1ß, tumor necrosis factor-, and lipopolysaccharide, but inhibited by dexamethasone. In contrast to PGE₂ 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.

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