The effect of mifepristone administration on leukocyte populations, matrix metalloproteinases 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 ripening in women throughout gestation. However, its mechanism of action is largely unknown. The aim of the study was to investigate the effect of in-vivo administration of mifepristone on inflammatory cells and mediators in the cervix. Cervical biopsies were taken from women undergoing a first trimester termination of pregnancy at 0, 6, 12, 24 and 36 h (n = 6 per group) after mifepristone administration. Biopsies were fixed for immunohistochemistry and also cultured for subsequent analysis of culture media by radioimmunoassay or enzyme-linked immunosorbent assay. After administration of mifepristone (6-24 h), there was an increase in immunostaining for leukocyte common antigen (CD45), neutrophil elastase, monocytes (CD68), and matrix metalloproteinases (MMP)-1, -8 and -9. Immunostaining for MMP-2 and tissue inhibitor of metalloproteinases (TIMP)-1, -2 and -4 were unaffected by mifepristone treatment. Secretion of monocyte chemotactic protein (MCP-1) was significantly (P < 0.05) increased from biopsies taken 6-24 h after mifepristone administration. Cervical biopsies also released interleukin-8 (IL-8), prostaglandin (PG) E(2), PGF(2alpha) and prostaglandin metabolites (PGEM and PGFM) although their secretion was unaffected by mifepristone treatment. This study suggests that mifepristone may, in part, effect cervical ripening by modulating the influx of inflammatory cells into the cervix, up-regulating MMP expression and inducing chemokine secretion by cervical tissue.
Denison
F C
FC
Obstetrics and Gynaecology, University of Edinburgh, UK.
Riley
S C
SC
Elliott
C L
CL
Kelly
R W
RW
Calder
A A
AA
Critchley
H O
HO
D000021:Abortifacient Agents, Steroidal / Q000494:pharmacology*; D000028:Abortion, Induced / Q000379:methods; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000187:drug effects / Q000378:metabolism; D019272:Leukocyte Elastase / Q000187:drug effects / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects*; D020782:Matrix Metalloproteinases / Q000187:drug effects* / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011453:Prostaglandins / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D000097382:CD68 Molecule
D000021:Abortifacient Agents, Steroidal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D018925:Chemokines; D017493:Leukocyte Common Antigens; D019272:Leukocyte Elastase; D020782:Matrix Metalloproteinases; D015735:Mifepristone; D011453:Prostaglandins; D019714:Tissue Inhibitor of Metalloproteinases; C067980:CD68 antigen, human; D000097382:CD68 Molecule