INDUCTION OF CERVICAL RIPENING W/ INTERLEUKIN 8 IN PREGNANT RHESUS MONKEYS

白细胞介素-8（IL-8）是一种细胞因子， 中性粒细胞趋化性和活化。 孕酮抑制和 抗孕激素刺激绒毛膜和蜕膜产生IL-8。 宫颈成熟与炎症细胞的流入有关 但IL-8在灵长类动物分娩中的作用仍然是 建立。 为了研究IL-8在宫颈成熟中的作用， 我们将纯化的人成纤维细胞来源的IL-8阴道内给药， 在3只妊娠猴中，从妊娠137-9天开始（期限= 167 天）。 宫颈通过改良的 Bishop=s得分。 IL-8在媒介物（2.5%HPC与300 μ l）中施用。 ? 1伊文思蓝溶液），将1.0或3.0 ml注射器插入到 阴道穹窿 每隔一段时间进行羊膜穿刺术， 羊水中前列腺素（PGs）和细胞因子的变化。 后 在4-5天的恢复期，第二剂量的IL-8（300 ng/kg）被施用。 管理。 结果分次剂量阴道给药 IL-8对改良Bishop=s评分（平均值？SEM）总结在 下表。 三分之二的动物表现出羊水增加， 羊水IL-8浓度无变化， PGE 2还是PGF 2？ 一只动物在第二剂IL-8后分娩。 剂量0小时24小时48小时72小时150 ng/kg 0.6？0.3 5.6？0.3* 5.0 ? 1.2* 5.3？0.3* 300纳克/千克2.0？1.0 4.0？3.0六点五？0.5* * 与时间0小时的差异为P<0.05（t检验）。 结论 纯化的人成纤维细胞来源的IL-8的阴道内应用 在晚期妊娠的恒河猴中诱导显著的宫颈成熟。 资助NIH HD 06159，东丽工业公司出版物Haluska GJ， Naruto M，Ida N，Cook MJ，Novy MJ. 促宫颈成熟 白细胞介素-8（IL-8）在妊娠恒河猴中的作用。 在社会上 第45届妇科调查计划和摘要年会 (held in Atlanta，GA，March 11-14，1998），p190 A（摘要#T615）。

Interleukin-8 (IL-8) is a cytokine that induces selective neutrophil chemotaxis and activation. Progesterone inhibits and antiprogestins stimulate production of IL-8 by chorion and decidua. Cervical ripening is associated with an influx of inflammatory cells into the cervix but the role of IL-8 in primate parturition remains to be established. To investigate the role of IL-8 in cervical ripening, we administered purified, human fibroblast-derived IL-8 intravaginally in 3 pregnant monkeys beginning at 137-9 days of gestation (term = 167 days) at a dose of 150 ng/kg. The cervix was evaluated by a modified Bishop=s Score. IL-8 was administered in vehicle (2.5% HPC with 300 ?l Evans Blue solution) by inserting a 1.0 or 3.0 ml syringe into the vaginal vault. Amniocentesis was performed at intervals to determine changes in amniotic fluid prostaglandins (PGs) and cytokines. After a recovery period of 4-5 days, a second dose of IL-8 (300 ng/kg) was administered. Res ults The effect of graded doses of intravaginal IL-8 on Modified Bishop=s Scores (mean ? SEM) is summarized in the table below. Two out of three animals showed an increase in amniotic fluid IL-8 concentrations but there were no changes in amniotic fluid PGE2 or PGF2?. One animal delivered after the second dose of IL-8. Dose 0 hours 24 hours 48 hours 72 hours 150 ng/kg 0.6 ? 0.3 5.6 ? 0.3* 5.0 ? 1.2* 5.3 ? 0.3* 300 ng/kg 2.0 ? 1.0 4.0 ? 3.0 6.5 ? 0.5* *different from time 0 hrs at P<0.05 (t-test). Conclusion Intravaginal application of purified human fibroblast-derived IL-8 induces significant cervical ripening in late pregnant rhesus monkeys. FUNDING NIH HD06159, Toray Industries Inc PUBLICATIONS Haluska GJ, Naruto M, Ida N, Cook MJ, Novy MJ. Induction of cervical ripening with interleukin-8 (IL-8) in pregnant rhesus monkeys. In Society for Gynecological Investigation Program and Abstracts 45th Annual Meeting (held in Atlanta, GA, March 11-14, 1998), p 190A (abstract #T615).