Cervical dilatation: induction by antigestagens via adhesion molecules. An in vitro examination in endothelial cell...

Cervical ripening at term resembles an inflammatory reaction with invasion of activated granulocytes into the cervical stroma. Our objective was to investigate the influence of the antigestagen onapristone alone and in combination with other substances associated with cervical ripening on the expression of the inflammation-associated adhesion molecules ELAM-1, ICAM-1 and VCAM-1. Human endothelial cell cultures were stimulated with onapristone (200 ng/ml), TNF-alpha (100 U/ml), IL-8 (20 ng/ml) and PGE2 (3 ng/ml) separately and in combination (n = 6). The expression of adhesion molecules was determined qualitatively and quantitatively by immunofluorescence staining and flow cytometry with statistical evaluation by Kolmogorov-Smirnov analysis. Onapristone upregulated slightly the expression of ELAM-1 (19%). The costimulation of onapristone and TNF-alpha provoked an additive expression of VCAM-1 (64%) beyond the effect of TNF-alpha alone, while the costimulation of onapristone and PGE2 as well as the combination with IL-8 did not result in an additional stimulatory effect. All results were statistically significant (p < 0.001). This result supports our hypothesis that onapristone may lead to an increased adhesion of granulocytes to the capillary endothelium thereby initiating cervical ripening.