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?
基本信息
- 批准号:6453687
- 负责人:
- 金额:$ 11.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:
项目摘要
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<;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。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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MICHAEL G GRAVETT其他文献
MICHAEL G GRAVETT的其他文献
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{{ truncateString('MICHAEL G GRAVETT', 18)}}的其他基金
AN EXPERIMENTAL MODEL FOR CHORIOAMNIONITIS AND PREMATURITY
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7561875 - 财政年份:2007
- 资助金额:
$ 11.11万 - 项目类别:
AN EXPERIMENTAL MODEL FOR CHORIOAMNIONITIS AND PREMATURITY
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7348889 - 财政年份:2006
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$ 11.11万 - 项目类别:
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7165203 - 财政年份:2005
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$ 11.11万 - 项目类别:
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$ 11.11万 - 项目类别:
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:
6592311 - 财政年份:2002
- 资助金额:
$ 11.11万 - 项目类别:
INTERLEUKIN 10 INHIBITS INTERLEUKIN 1? INDUCED PRETERM LABOR IN RHESUS MONKEYS
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