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 to 3 pregnant monkeys beginning at 137-139 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% hydroxypropyl cellulose [HPC] with 300 fl 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 and cytokines. After a recovery period of 4-5 days, a second dose of IL-8 (300 ng/kg) was administered. The effect of graded doses of intravaginal IL-8 on modified Bishop's Scores (mean q SEM) Dose 0 hours 24 hours 48 hours 72 hours 150 ng/kg 0.6 q 0.3 5.6 q 0.3* 5.0 q 1.2* 5.3 q 0.3* 300 ng/kg 2.0 q 1.0 4.0 q 3.0 6.5 q 0.5* * different from time 0 hrs at P<0.05 (t-test). 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. Intravaginal application of purified human fibroblast-derived IL-8 induces significant cervical ripening in late pregnant rhesus monkeys. This data may have important implications in therapies related to induction of cervical ripening and labor.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000163-39
Application #
6277370
Study Section
Project Start
1998-05-01
Project End
1999-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
39
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Oregon Regional Primate Research Center
Department
Type
DUNS #
City
Beaverton
State
OR
Country
United States
Zip Code
97006
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