BIOCHEMICAL-CHANGES IN THE CERVICAL TISSUE OF RABBIT INDUCED BY INTERLEUKIN-8, INTERLEUKIN-1-BETA, DEHYDROEPIANDROSTERONE-SULFATE AND PROSTAGLANDIN E(2) - A COMPARATIVE-STUDY

The aim of this research was to study and compare the mechanism of act ion of interleukin (IL)-8, IL-1 beta dehydroepiandrosterone sulphate ( DHEA-S) and prostaglandin (PG)E(2) on the cervix. Five equal groups of pregnant rabbits (n = 45) were tested by either placebo or tested dru gs in the form of vaginal suppositories once daily for 3 days. The sup positories contained human recombinant IL-8 (100 ng), IL-1 beta (200 n g), DHEA-S (10 mg) or PGE(2) (1 mg). All rabbits were tested by one do se, two doses or three doses. Consistency, dilatation and water conten ts were estimated 24 h after the last dose of treatment, Leukocyte inf iltration of the cervices was studied after staining the cervical tiss ue sections with antirabbit RT2 monoclonal antibodies. Relative collag en concentration was assessed after staining with Picrosirius Red. Col lagenase, gelatinase and elastase activities were measured in 100 mg o f homogenized cervical connective tissue. Water contents were signific antly increased in all tested cervices. Neutrophil numbers were increa sed in IL-8 and IL-1 beta groups after the second dose of treatment (P < 0.0005 and 0.001 respectively). In the PGE(2) group, neutrophils we re increased after the third dose of treatment, whereas in DHEA-S grou p no significant changes were observed. Collagen content was significa ntly decreased in IL-8, IL-1 beta and PGE(2) groups after the first do se of treatment (P < 0.004, and 0.005 and 0.03 respectively). In the D HEA-S group, the decrease in collagen content occurred after the third dose (P < 0.05). Collagenase activity was markedly increased in IL-8, IL-1, and DHEA-S groups after the second dose of treatment (P < 0.001 , 0.003 and 0.007 respectively). No significant increase in collagenas e activity was found in PGE(2) group. Gelatinase activity was signific antly increased in IL-8, IL-1 beta, PGE(2) and DHEA-S groups after the second dose of treatment (P < 0.008, 0.01, 0.003 and 0.05 respectivel y). Also, elastase activity was increased after the second dose of tre atment in all groups (P < 0.001, 0.001 0.001 and 0.006 respectively). Our data suggest that ripening of the cervix in rabbit can be initiate d by different mechanisms. Cytokines play a vital role in cervical rip ening, especially IL-8 and IL-1. IL-8 is one of the factors which coul d ripen the cenix in a manner similar to the physiological process at term.