INTERLEUKIN 10 INHIBITS INTERLEUKIN 1? INDUCED PRETERM LABOR IN RHESUS MONKEYS

白细胞介素 10 抑制白细胞介素 1？

• 批准号: 6116159
• 负责人: MICHAEL G GRAVETT
• 金额: $ 9.03万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-15 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116159
• 关键词: Mammalia; bacteria; clinical research; communicable diseases; endocrine gland /system; immunology; infant mortality; inflammation; low birth weight infant human; mother /infant health care; reproductive system; women's health

Proinflammatory cytokines including interleukin-1? (IL-1?) play a central role in the pathophysiology of infection-induced preterm labor. Interleukin-10 (IL-10), an antiinflammatory cytokine, leads to deactivation of macrophages and inhibits the production of proinflammatory cytokines. We utilized pregnant rhesus monkeys with timed gestations to investigate the hypothesis that IL-10 may inhibit preterm uterine contractions induced by IL-1?. Study Design. Four chronically instrumented pregnant rhesus macaques at 135 days of gestation (term is 167 days) were given intravenous (25 ?g/kg 3 times daily) and intraamniotic (100 ?g 3 times daily) infusions of recombinant IL-10 for three days. After the first dose, animals received intraamniotic infusions of 10 ?g of IL-1? (which we have previously established to reliably stimulate uterine contractility). For comparison, 7 days and 14 days after combined IL-10 and IL-1? infusion, each animal received repeat intraamniot ic i nfusions of IL-1? without IL-10. Uterine contractility (HCA; hourly contraction area), and amniotic fluid (AF) concentrations of IL-1?, IL-10, TNF, prostaglandins E2 (PGE2) and F2? (PGF2?) were serially determined before, during, and after each infusion. Results. Treatment with IL-10 significantly reduced IL-1? induced uterine contractility when administered concurrently with IL-1? (by 85%, *p<0.05), when compared to IL-1? infusion alone 14 days later, when AF IL-10 was no longer detected. Between 0 and 14 days, an inverse relationship was noted between AF IL-10 concentrations and uterine contractility. IL-10 was detected within AF for a minimum of 7 days following IL-10 infusion. The terminal-phase half-life of AF IL-10 was 14 hours. No adverse reactions were noted during IL-10 infusion. Median Peak AF Concentration (ng/ml) Peak Uterine Contractility Event IL-1? IL-10 TNF PGE2 PGF2? (HCA; mmHg?sec/hr) Baseline 0 0 0 0.26 0.15 2600 IL-1? + IL-10 35.3 106.8 460 6.4 0.78 1,800* IL-1? alone + 14d 38.6 0 859 7.7 1.5 11,650 Conclusions. We conclude that IL-10 effectively inhibits IL-1? induced preterm uterine contractility, and may represent a useful adjunct in the treatment of infection-induced preterm labor. FUNDING NIH AI42490, HD06159 PUBLICATIONS Gravett MG, Novy MJ, Haluska GJ, Sadowsky DW, Cook MJ, Witkin SS. Interleukin-10 (IL-10) inhibits interleukin-1? (IL-1?), induced preterm labor in rhesus monkeys. Infect Dis Obstet Gynecol 6:77-78, 1998.

促炎细胞因子包括白细胞介素-1？ (IL-1?)发挥 在感染性早产病理生理学中的核心作用 劳动 白细胞介素-10（IL-10）是一种细胞因子， 灭活巨噬细胞并抑制 促炎细胞因子 我们利用怀孕的恒河猴， 定时妊娠以研究IL-10可能抑制 IL-1诱导的子宫提前收缩。 研究设计. 四 在135天的慢性仪器妊娠恒河猴 妊娠期（167天）静脉注射（25？g/kg 3倍 每日）和羊膜腔内（100？g每日3次）输注 重组IL-10三天。 第一次给药后，动物 接受羊膜腔内输注10？IL-1？ （我们有） 先前建立的可靠刺激子宫收缩性）。 为了比较，7天和14天后，联合IL-10和IL-1？ 输注后，每只动物接受重复静脉内输注 IL-1？ 没有IL-10。 子宫收缩力（HCA;每小时收缩 面积）和羊水（AF）中IL-1？浓度，IL-10，TNF， 前列腺素E2（PGE 2）和F2？ (PGF2?)连续测定 在每次输注之前、期间和之后。 结果 治疗 IL-10显著降低IL-1？ 诱导子宫收缩力， 与IL-1同时给药？ (by 85%，*p<0.05），比较时 IL-1？ 14天后，当AF IL-10不再 检测到 在0和14天之间，注意到反向关系 AF IL-10浓度和子宫收缩力之间的关系。 IL-10的 在IL-10输注后至少7天内检测到AF。 AF IL-10的终末相半衰期为14小时。 无不良 在IL-10输注期间观察到反应。 中位峰值AF 浓度（ng/ml）峰值子宫收缩事件IL-1？ IL-10 TNF PGE2 PGF2？ (HCA; mmHg？秒/小时）基线0 0 0 0. 26 0. 15 2600 IL-1？ + IL-10 35.3 106.8 460 6.4 0.78 1，800 * IL-1？ 单独+14 d 38.6 0 859 7.7 1.5 11，650结论。 我们得出结论，IL-10有效地 抑制IL-1？ 诱导早产子宫收缩，并可能 在治疗感染引起的 早产 资助NIH AI 42490，HD 06159出版物Gravett MG， Novy MJ，Haluska GJ，Sadowsky DW，Cook MJ，Witkin SS. 白细胞介素-10 （IL-10）抑制白细胞介素-1？ (IL-1?),早产儿引产 恒河猴 Infect Dis Obstet Gynecol 6：77-78，1998.