INTERLEUKIN 10 INHIBITS PRETERM UTERINE CONTRACTIONS INDUCED BY INTERLEUKIN 1

白细胞介素 10 抑制白细胞介素 1 引起的早产子宫收缩

• 批准号: 6277398
• 负责人: MICHAEL G GRAVETT
• 金额: $ 7.42万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277398
• 关键词: Mammalia; Primates; bacteria; clinical research; endocrine gland /system; immunology; infant mortality; infection; inflammation; low birth weight infant human; mother /infant health care; reproductive system; women's health

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.

促炎细胞因子包括白细胞介素-1b（IL-1b）和 由TH 1炎症细胞产生的肿瘤坏死因子（TNF）， 在刺激子宫收缩力方面的核心作用， 感染引起的早产 我们之前已经证明， 羊膜腔内输注重组人IL-1b诱导早产 怀孕恒河猴的子宫收缩 白细胞介素-10，一种天然的 存在的TH 2细胞因子，已经在体外证明， 下调促炎细胞因子的许多作用 包括IL-1b和TNF，并可能在维持体内平衡中发挥作用 怀孕期间 我们利用4只长期使用仪器的恒河猴 用定时妊娠来研究IL-10会 在体内抑制IL-1诱导的早产子宫收缩。 动物 在妊娠135天时， 输注人IL-10（25 fg/kg，每日3次，100 fg，一次 每日一次，持续3天）。 在此治疗期间， 动物也被给予羊膜内输注10 FG人 IL-1b，我们之前已经证明可以可靠地刺激 子宫收缩和分娩。 子宫收缩力（H.A.;小时 收缩面积），和羊水（AF）中IL-10的浓度， 连续检测IL-1、TNF和前列腺素E2（PGE 2）水平 在输注之前、期间和之后。 IL-10治疗后14天 + IL-1b输注，每只动物接受另一次羊膜内输注 单独IL-1b，作为对照。 同时治疗 IL-10显著降低AF中TNF、PGE 2和TNF-α的浓度。 子宫收缩力，当与单独输注IL-1b相比时，在所有4个 动物，尽管同样高AF浓度的IL-1b在两个 组 中位AF浓度（pg/ml）HCA事件IL-1b TNF PGE2（mmHg.sec/hr）IL-1b + IL-10 41，000 375 7，600 4，375单独IL-1b 33，000 1，325 12，700> 20，000未发现不良反应 IL-10治疗期间4只动物。 我们得出结论，IL-10 下调IL-1诱导的早产子宫收缩力， 用于治疗感染引起的早产， 交付.