Labor-associated changes in interleukin-10 production and its regulation by immunomodulators in human choriodecidua.
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-1beta (10 ng/mL), tumor necrosis factor-alpha (100 ng/mL), lipopolysaccharide (5 microg/mL), dexamethasone (1 micromol/ 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-1beta, tumor necrosis factor-alpha, 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.
Simpson
K L
KL
Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, New Zealand.
Keelan
J A
JA
Mitchell
M D
MD
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000328:Adult; D002823:Chorion / Q000378:metabolism*; D003656:Decidua / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D007743:Labor, Obstetric / Q000378:metabolism*; D011247:Pregnancy
D000276:Adjuvants, Immunologic; D005938:Glucocorticoids; D018836:Inflammation Mediators; D015850:Interleukin-6; D016753:Interleukin-10; D003907:Dexamethasone; D015232:Dinoprostone