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


METHODS
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.


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Texas Medical Branch, Galveston 77550-1062, USA.
Holger
H
Maul
Leili
L
Shi
Stephen G
SG
Marx
Robert E
RE
Garfield
George R
GR
Saade
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D020070:Cervical Ripening / Q000187:drug effects*; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology*; D007752:Obstetric Labor, Premature / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011247:Pregnancy; D011372:Progestins / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D006727:Hormone Antagonists; D008070:Lipopolysaccharides; D010975:Platelet Aggregation Inhibitors; D011372:Progestins; D014230:Triazoles; D015735:Mifepristone; C063964:bepafant