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

Parturition is associated with increased production of proinflammatory medi ators 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 membrane s obtained at term by cesarean section before labor (n = 6-7) or after spon taneous 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 i mmunoassay. Basal choriodecidual production rates of IL-10 mere significant ly decreased with labor (P < 0.001), whereas PGE(2) and IL-6 production rat es 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 inc reased responsiveness of IL-10 production to inflammatory stimuli after lab or, but decreased responsiveness to the inhibitory effects of dexamethasone . These data indicate that IL-10 could play a role in modulating or promoti ng resolution of the inflammatory processes associated with labor at term a nd with intrauterine infection-associated preterm labor. Media were harvest ed, and IL-10, IL-6, and PGE(2) concentrations were determined by immunoass ay. Basal choriodecidual production rates of IL-10 mere significantly decre ased with labor (P < 0.001), whereas PGE(2) and IL-6 production rates incre ased. The production of all three substances was increased by IL-1 beta, tu mor necrosis factor-alpha, and lipopolysaccharide, but inhibited by dexamet hasone. In contrast to PGE(2) and IL-6, there was significantly increased r esponsiveness 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 resol ution of the inflammatory processes associated with labor at term and with intrauterine infection-associated preterm labor.