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: 6453687
• 负责人: MICHAEL G GRAVETT
• 金额: $ 11.11万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6453687
• 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.

包括白介素1在内的促炎细胞因子？(IL-1？)播放 感染性早产的病理生理学中心作用 劳力。白介素10(IL-10)，一种抗炎细胞因子，导致 使巨噬细胞失活并抑制其产生 促炎细胞因子。我们利用怀孕的恒河猴 研究IL-10可能抑制的假说的计时妊娠 IL-1诱导的早产子宫收缩。研究设计。四 妊娠135天的恒河猴 妊娠(足月167天)静脉滴注(25g/kg)3次 每日)和羊膜腔内(100g，每天3次)输注 重组IL-10治疗3天。在第一次注射后，动物 羊膜腔内输注IL-1、IL-110g。(我们有 以前建立的可靠地刺激子宫收缩的药物)。 比较IL-10和IL-1联合应用后7天和14天？ 输液，每只动物接受重复的羊膜腔内注射 IL-1？没有IL-10。子宫收缩能力(Hca；每小时收缩 羊水中IL-1、IL-10、肿瘤坏死因子、 前列腺素E2(PGE2)和F2？(PGF2？)是连续确定的 在每次输液之前、期间和之后。结果。通过以下方式治疗 IL-10显著降低IL-1？在以下情况下诱发子宫收缩 与IL-1同时使用？(下降85%，*p&lt；0.05) 白介素1？14天后单独输液，当AF IL-10不再 检测到。在0至14天之间，注意到了相反的关系 AF IL-10浓度与子宫收缩功能之间的关系。IL-10是 在注射IL-10后至少7天内在房颤内检测到。 AF IL-10的终末半衰期为14小时。没有不利的影响 在输注IL-10的过程中观察到了反应。中峰值自动对焦 浓度(ng/ml)峰值子宫收缩事件IL-1？IL-10 肿瘤坏死因子-前列腺素E_2-前列腺素F2？(HCA；毫米汞？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+14d 38.6 0859 7.7 1.5 11,650个结论。我们得出结论：IL-10有效地 抑制IL-1？诱发早产子宫收缩，并可能 是治疗感染所致疾病的有效辅助手段 早产。资助NIH AI42490，HD06159出版物Gravett MG， NOVY MJ，Haluska GJ，Sadowsky DW，Cook MJ，Witkin SS。白介素10 白介素10抑制白介素1？(IL-1？)，诱导早产 恒河猴。感染妇科疾病6：77-78,1998。