Platelet-activating factor antagonist WEB-2170 inhibits lipopolysaccharide-induced, but not antiprogestin-induced, preterm cervical ripening in timed-pregnant rats

Abstract

Objective The purpose of this study was to determine whether the platelet-activating factor antagonist WEB-2170 inhibits preterm cervical ripening induced by lipopolysaccharide or by antiprogestin RU 486. Study design Timed-pregnant rats were killed on day 16 after treatment with (1) WEB-2170, lipopolysaccharide, lipopolysaccharide plus WEB-2170, or vehicle control and (2) with WEB-2170, RU 486, RU 486 plus WEB-2170, or vehicle control. Cervical ripening was assessed by light-induced fluorescence and resistance to stretch. Statistics were assessed by 1-way analysis of variance followed by Tukey-test ( P < .05). Results Light-induced fluorescence and resistance to stretch were significantly lower in the lipopolysaccharide-treated and in the RU486-treated animals compared with vehicle control (lipopolysaccharide:light-induced fluorescence, 7.0±0.6 vs 12.8±0.8 [ P = .001]; resistance to stretch, 0.41±0.03 N/mm vs 0.54±0.04 N/mm [ P < .05]; RU486:light-induced fluorescence, 9.6±0.6 vs 11.7±0.6 [ P < .05]; resistance to stretch, 0.28±0.06 N/mm vs 0.61±0.02 N/mm [ P < .001]). Compared with vehicle control, WEB-2170 alone did not alter cervical light-induced fluorescence or resistance to stretch. Although WEB-2170 significantly blocked cervical ripening after lipopolysaccharide administration (light-induced fluorescence, 11.3±1.3 [ P < .05]; resistance to stretch, 0.61±0.04 [ P < .01]), WEB-2170 did not inhibit the RU 486–induced cervical ripening. Conclusion Although infection-related cervical ripening is inhibited by platelet-activating factor antagonists, the physiologic process of cervical ripening appears to be unaffected. Platelet-activating factor inhibition may be of clinical value in the infection-related pathologic processes that are responsible for premature cervical ripening.