interleukin-8 and onapristone

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.

Topics: Cell Adhesion Molecules; Cells, Cultured; Cervix Uteri; Dinoprostone; E-Selectin; Endothelium, Vascular; Female; Fluorescent Antibody Technique, Indirect; Gonanes; Hormone Antagonists; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Labor Stage, First; Labor, Induced; Pregnancy; Tumor Necrosis Factor-alpha; Umbilical Veins; Vascular Cell Adhesion Molecule-1

Our purpose was to assess the effects of labor and antigestagens on production of interleukin 8 by the term human placenta and to localize interleukin 8 in first- and third- trimester placentas.. The study was conducted by the Department of Obstetrics and Gynaecology of the University of Edinburgh. Five placentas were collected after spontaneous and cesarean deliveries. Explants were cultured in the presence of mifepristone, lilopristone, or onapristone. The production of interleukin 8 was determined by specific radioimmunoassay, and the immunolocalization of interleukin 8 was determined in sections of first- and third-trimester placentas.. All explants produced interleukin 8. Production was significantly increased (P < .05) after spontaneous delivery. In placentas delivered spontaneously, onapristone significantly increased production of interleukin 8 (P < .05), whereas in those from cesarean deliveries lilopristone caused a significant increase in production (P < .05). In the third-trimester placenta interleukin 8 was localized in the perivascular area of fetal vessels. In first-trimester villi it was peripherally located in syncytiotrophoblast.. The human placenta at term is capable of producing interleukin 8, which is localized around the perivascular area of the villi. Production is increased after spontaneous labor and to varying degrees by the antigestagens studied. Interleukin 8 may have a role in the onset of parturition by recruiting and activating neutrophils at the placental site.

Topics: Culture Techniques; Estrenes; Female; Gonanes; Hormone Antagonists; Humans; Immunohistochemistry; Interleukin-8; Labor, Obstetric; Mifepristone; Placenta; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Third; Progestins