INTERLEUKIN 10 INHIBITS PRETERM UTERINE CONTRACTIONS INDUCED BY INTERLEUKIN 1

促炎症细胞因子，包括白介素1b(IL-1b)和 由TH1炎症细胞产生的肿瘤坏死因子(TNF)发挥作用 在刺激子宫收缩中的核心作用与 感染导致的早产。我们之前已经证明过 羊膜腔内输注重组人IL-1b诱导早产 怀孕恒河猴的宫缩。白介素10，一种天然的 产生TH2细胞因子，已在体外被证明 下调促炎症细胞因子的许多作用 包括IL-1b和肿瘤坏死因子，可能在维持体内平衡中发挥作用 在怀孕期间。我们利用了4只长期使用仪器的恒河猴 来研究IL-10将 在体内抑制IL-1诱导的早产子宫收缩。动物 在怀孕135天时给予静脉注射和羊水注射 人IL-10(25fg/kg，每日3次，100fg/次)输注 每天，分别为3天)。在这一治疗期间， 动物也被给予10FG人的羊膜内输液 IL-1b，我们之前已经证明了它可以可靠地刺激 子宫收缩和分娩。子宫收缩能力(H.A.；每小时 宫缩面积)和羊水(AF)中IL-10浓度， 连续测定IL-1、肿瘤坏死因子、前列腺素E_2 输液前、输液中和输液后。在IL-10治疗后14天 IL-1b输注，每只动物接受另一次羊膜内输液 单独使用IL-1b作为对照。同时治疗与 IL-10显著降低房颤患者血清中肿瘤坏死因子、前列腺素E_2和 子宫收缩能力，与单独输注IL-1b相比，所有4个 动物，尽管两者的房颤中IL-1b浓度相似 群组 房颤中位数。(pg/ml)HCA事件IL-1b肿瘤坏死因子 前列腺素E_2(毫米波/秒/小时)IL-1b IL-10 41,000 375 7,600 4,375 IL-1b单独 33,000 1,325 12,700；20,000例患者中未发现不良反应 4只动物接受IL-10治疗。我们得出结论，IL-10 下调IL-1诱导的早产子宫收缩能力 在治疗感染引起的早产和 送货。

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.