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

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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).