INTERLEUKIN 10 INHIBITS PRETERM UTERINE CONTRACTIONS INDUCED BY INTERLEUKIN 1

促炎细胞因子包括白细胞介素-1b （IL-1b）和

Proinflammatory cytokines including interleukin-1b (IL-1b) and tumor necrosis factor (TNF), produced by TH1 inflammatory cells, play a central role in stimulating uterine contractility associated with infection-induced preterm labor. We have previously demonstrated that intraamniotic infusion of human recombinant IL-1b induces preterm contractions in pregnant rhesus monkeys. Interleukin-10, a naturally occurring TH2 cytokine, has been demonstrated in vitro to down-regulate many of the effects of the proinflammatory cytokines including IL-1b and TNF and may play a role in maintaining homeostasis in pregnancy. We utilized 4 chronically-instrumented rhesus macaques with timed gestations to investigate the hypothesis that IL-10 will inhibit preterm uterine contractions induced by IL-1 in vivo. Animals at 135 days of gestation were given intravenous and intraamniotic infusions of human IL-10 (25 fg/kg 3 times daily and 100 fg once daily, respectively, for 3 days). During this treatment period, animals were also given an intra amniotic infusion of 10 fg human IL-1b, which we have previously demonstrated to reliably stimulate uterine contractions and labor. Uterine contractility (H.A.; hourly contraction area), and amniotic fluid (AF) concentrations of IL-10, IL-1, TNF, and prostaglandin E2 (PGE2) were determined serially before, during, and after infusions. At 14 days after IL-10 treatment + IL-1b infusion, each animal received another intraamniotic infusion of IL-1b alone, to serve as a control. Concurrent treatment with IL-10 significantly reduced AF concentrations of TNF, PGE2, and uterine contractility, when compared to IL-1b infusion alone in all 4 animals, despite similarly high AF concentrations of IL-1b in both groups Median AF Conc. (pg/ml) HCA Event IL-1b TNF PGE2 (mmHg.sec/hr) IL-1b + IL-10 41,000 375 7,600 4,375 IL-1b alone 33,000 1,325 12,700 >20,000 No adverse reactions were noted among the 4 animals during IL-10 treatment. We conclude that IL-10 down-regulates IL-1 induced preterm uterine contractility and may be useful in the treatment of infection-induced preterm labor and delivery.