Baggia S, Gravett M G, Witkin S S, Haluska G J, Novy M J
Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006, USA.
J Soc Gynecol Investig. 1996 May-Jun;3(3):121-6. doi: 10.1177/107155769600300304.
To describe the temporal and quantitative consequences of intra-amniotic interleukin-1 beta infusion in a nonhuman primate model.
On days 128-138 of gestation (term 167 days), four chronically instrumented rhesus monkeys (Macaca mulatta) underwent serial intra-amniotic infusions of 2, 5, and 10-20 micrograms recombinant human interleukin-1 beta. Each infusion was for 2 hours, and subsequent infusions were at least 48 hours later. Amniotic fluid was sampled serially both before and after infusion for interleukin-1 beta, tumor necrosis factor-alpha (TFN-alpha), and prostaglandin (PG) E2 and F2 alpha by specific assays, and uterine activity in each monkey was recorded continuously.
Intra-amniotic concentrations of interleukin-1 beta rose dramatically after infusion. This rise was rapidly followed by the appearance of TNF-alpha in the amniotic cavities of all animals, with maximal levels reached 5 hours after the initiation of the infusion. Both interleukin-1 beta and TNF-alpha were rapidly cleared from the amniotic fluid and returned to baseline levels by 24-48 hours. Increases in PGE2 and F2 alpha paralleled those of the two cytokines but remained elevated for the duration of the experiments. The stimulation of uterine contractility from a pre-infusion level of 200 mmHg. seconds/hour to 6000 mmHg. seconds/hour occurred an average of 6-10 hours after interleukin-1 beta infusion. These stimulations were transient, usually abating by 22 hours after infusion, and did not result in frank labor.
In the rhesus monkey, intra-amniotic infusion of interleukin-1 beta rapidly induces production of intra-amniotic TNF-alpha as well as PGE2 and F2 alpha, followed by uterine contractility. Uterine activity diminishes as cytokine levels return to pre-infusion levels, even in the presence of elevated intraamniotic PG levels. Tumor necrosis factor-alpha may act synergistically with interleukin-1 beta in the pathophysiology of cytokine-related preterm labor.
描述在非人类灵长类动物模型中羊膜腔内注入白细胞介素-1β的时间和定量结果。
在妊娠128 - 138天（足月为167天）时，对4只长期植入仪器的恒河猴（猕猴）进行羊膜腔内连续注入2、5和10 - 20微克重组人白细胞介素-1β。每次注入持续2小时，后续注入至少在48小时后进行。在注入前后连续采集羊水样本，通过特定检测方法检测白细胞介素-1β、肿瘤坏死因子-α（TNF-α）、前列腺素（PG）E2和F2α，并持续记录每只猴子的子宫活动情况。
注入后羊膜腔内白细胞介素-1β浓度急剧上升。随后所有动物羊膜腔内迅速出现TNF-α，在注入开始后5小时达到最高水平。白细胞介素-1β和TNF-α均迅速从羊水中清除，在24 - 48小时后恢复到基线水平。PGE2和F2α的增加与这两种细胞因子的增加平行，但在实验期间一直保持升高。子宫收缩力从注入前的200mmHg·秒/小时刺激到6000mmHg·秒/小时，平均在白细胞介素-1β注入后6 - 10小时出现。这些刺激是短暂性的，通常在注入后22小时减弱，且未导致真正的分娩。
在恒河猴中，羊膜腔内注入白细胞介素-1β可迅速诱导羊膜腔内TNF-α以及PGE2和F2α的产生，随后引起子宫收缩。即使羊膜腔内PG水平升高，随着细胞因子水平恢复到注入前水平，子宫活动也会减弱。肿瘤坏死因子-α可能在细胞因子相关早产的病理生理过程中与白细胞介素-1β协同作用。
