INDUCTION OF HEAT SHOCK PROTEIN BY INTERLEUKIN 1 INTRAAMNIOTIC INFUSION

诱导炎性细胞因子合成导致 前列腺素的产生和子宫肌层收缩是一个既定的 感染相关早产的途径。限制机制 细胞因子诱导的早产直到最近才 调查过了。白介素1受体拮抗剂 在羊水(AF)中发现，并显示增加 细胞因子激活后的浓度。我们现在为您报道 向房颤内注入IL-1也可诱导热休克的合成 蛋白质(HSP)。热休克蛋白基因转录的诱导已被证明 抑制IL-1和肿瘤坏死因子的转录 基因。计时妊娠的慢性仪器化猕猴 输注重组人IL-1b。以定时间间隔AF是 测定IL-1、TNF、IL-6浓度。 60kD热休克蛋白水平用单抗用EIA法测定 人热休克蛋白抗体。羊水也进行了检测 Western blotting检测到60kD和70kD热休克蛋白的存在。在输液前， 房颤患者未检测到肿瘤坏死因子、IL-6和热休克蛋白。在注射IL-1后， 房颤患者血清肿瘤坏死因子和白介素6水平迅速升高。房颤患者出现60kD热休克蛋白 与羊水中肿瘤坏死因子和肿瘤坏死因子的浓度下降相一致 IL-6。在4只猴子中，AF HSP的峰值浓度为1-5 ng/ml 使用人热休克蛋白生成的标准曲线进行估计。西式 印迹分析证实房颤患者在IL-1之前不存在HSP 房颤后60kD和70kD热休克蛋白的输注和出现 输液。因此，羊膜腔内热休克蛋白合成的诱导 促炎症细胞因子可能是另一种限制 细胞因子合成和随后导致早产的级联反应 宫缩。

Induction of proinflammatory cytokine synthesis leading to prostaglandin production and myometrial contractions is an established pathway of infection-related preterm labor. The mechanisms limiting cytokine-induced preterm contractions have only recently been investigated. Interleukin-1 (IL-1) receptor antagonist has been identified in amniotic fluid (AF) and shown to increase in concentration following cytokine activation. We now report that infusion of IL-1 into the AF also induces synthesis of heat shock protein (HSP). Induction of HSP gene transcription has been shown to inhibit transcription of the IL-1 and tumor necrosis factor (TNF) genes. Chronically instrumented rhesus macaques with timed gestations were infused with recombinant human IL-1b. At timed intervals AF was obtained and IL-1, TNF, and IL-6 concentrations were determined. Levels of the 60kD HSP were determined by EIA using monoclonal antibodies to human HSP. Amniotic fluid was also tested for the presence of 60kD and 70kD HSP by Western blots. Prior to infusion, TNF, IL-6, and HSP were undetectable in AF. Following IL-1 infusion, AF TNF and IL-6 levels quickly rose. A 60kD HSP appeared in AF coincident with decreasing intraamniotic concentrations of TNF and IL-6. In 4 monkeys, peak AF HSP concentrations of 1-5 ng/ml were estimated using a standard curve generated with human HSP. Western blot analysis confirmed the absence of HSP in AF prior to IL-1 infusion and the appearance of 60kD and 70kD HSP in AF following infusion. Thus, induction of HSP synthesis in the amniotic cavity by proinflammatory cytokines may be another regulatory mechanism to limit cytokine synthesis and the subsequent cascade leading to preterm contractions.