Cervical ripening with the cytokines interleukin 8, interleukin 1 beta and tumour necrosis factor alpha in guinea-pigs.

It has been suggested that the collagenolytic enzymes released from white blood cells which infiltrate the pregnant human uterine cervix at term are responsible for connective tissue changes which take place during the ripening process. Similarly, an infiltration of inflammatory cells occurs in pregnant guinea-pigs either spontaneously at term or at preterm after treatment with the antiprogestin onapristone. The objective of this study was to evaluate the effects of the inflammatory cytokines interleukin 8 (IL-8), interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and a combination of IL-1 beta and TNF-alpha on cervical ripening in guinea-pigs during advanced pregnancy. The cytokines were applied locally (intracervically) in a gel for 2 days and the effects were assessed on the third day by both extensibility measurements and morphological evaluation. IL-8 treatment on days 42 and 43 post coitum (p.c) and on days 48 and 49 p.c. (term: day 67 +/- 3 p.c.) significantly (P < 0.05) increased cervical extensibility at both stages of pregnancy. Although IL-1 beta treatment (days 42 and 43 p.c.) led to a slight increase in cervical extensibility, this effect was not statistically significant. An electron microscope study performed on days 48 and 49 p.c. revealed a pronounced cervical ripening accompanied by the dissolution of collagen fibres, stromal oedema and the infiltration of polymorphonuclear leukocytes in all cytokine-treated groups. The morphological effects of IL-8 and IL-1 beta were indistinguishable from those observed during normal cervical ripening at term.(ABSTRACT TRUNCATED AT 250 WORDS)