The effect of mifepristone administration on leukocyte populations, matrixmetalloproteinases and inflammatory mediators in the first trimester cervix

Cervical ripening is analogous to an inflammatory reaction characterized by an influx of inflammatory cells and an increase in inflammatory mediators. The anti-gestogen mifepristone is highly effective in inducing cervical ri pening in women throughout gestation. However, its mechanism of action is l argely unknown. The aim of the study was to investigate the effect of in-vi vo administration of mifepristone on inflammatory cells and mediators in th e cervix. Cervical biopsies were taken from women undergoing a first trimes ter termination of pregnancy at 0, 6, 12, 24 and 36 h (n = 6 per group) aft er mifepristone administration. Biopsies were fixed for immunohistochemistr y and also cultured for subsequent analysis of culture media by radioimmuno assay or enzyme-linked immunosorbent assay. After administration of mifepri stone (6-24 h), there was an increase in immunostaining for leukocyte commo n antigen (CD45), neutrophil elastase, monocytes (CD68), and matrix metallo proteinases (MMP)-1, -8 and -9. Immunostaining for MMP-2 and tissue inhibit or of metalloproteinases (TIMP)-1, -2 and -4 were unaffected by mifepriston e treatment. Secretion of monocyte chemotactic protein (MCP-1) was signific antly (P < 0.05) increased from biopsies taken 6-24 h after mifepristone ad ministration. Cervical biopsies also released interleukin-8 (IL-8), prostag landin (PG) EP2, PGF(2 alpha) and prostaglandin metabolites (PGEM and PGFM) although their secretion was unaffected by mifepristone treatment. This st udy suggests that mifepristone may, in part, effect cervical ripening by mo dulating the influx of inflammatory cells into the cervix, up-regulating MM P expression and inducing chemokine secretion by cervical tissue.