Biochemical changes in the cervical tissue of rabbit induced by interleukin-8, interleukin-1beta, dehydroepiandrosterone sulphate and prostaglandin E2: a comparative study.
The aim of this research was to study and compare the mechanism of action of interleukin (IL)-8, IL-1beta dehydroepiandrosterone sulphate (DHEA-S) and prostaglandin (PG)E2 on the cervix. Five equal groups of pregnant rabbits (n = 45) were tested by either placebo or tested drugs in the form of vaginal suppositories once daily for 3 days. The suppositories contained human recombinant IL-8 (100 ng), IL-1beta (200 ng), DHEA-S (10 mg) or PGE2 (1 mg). All rabbits were tested by one dose, two doses or three doses. Consistency, dilatation and water contents were estimated 24 h after the last dose of treatment. Leukocyte infiltration of the cervices was studied after staining the cervical tissue sections with antirabbit RT2 monoclonal antibodies. Relative collagen concentration was assessed after staining with Picrosirius Red. Collagenase, gelatinase and elastase activities were measured in 100 mg of homogenized cervical connective tissue. Water contents were significantly increased in all tested cervices. Neutrophil numbers were increased in IL-8 and IL-1beta groups after the second dose of treatment (P < 0.0005 and 0.001 respectively). In the PGE2 group, neutrophils were increased after the third dose of treatment, whereas in DHEA-S group no significant changes were observed. Collagen content was significantly decreased in IL-8, IL-1beta and PGE2 groups after the first dose of treatment (P < 0.004, and 0.005 and 0.03 respectively). In the DHEA-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 collagenase activity was found in PGE2 group. Gelatinase activity was significantly increased in IL-8, IL-1beta, PGE2 and DHEA-S groups after the second dose of treatment (P < 0.008, 0.01, 0.003 and 0.05 respectively). Also, elastase activity was increased after the second dose of treatment 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 initiated by different mechanisms. Cytokines play a vital role in cervical ripening, especially IL-8 and IL-1. IL-8 is one of the factors which could ripen the cervix in a manner similar to the physiological process at term.
El Maradny
E
E
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handa-cho, 431-31 Hamamatsu, Japan.
Kanayama
N
N
Halim
A
A
Maehara
K
K
Sumimoto
K
K
Terao
T
T
D000818:Animals; D001834:Body Water / Q000378:metabolism; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology*; D007700:Kinetics; D007958:Leukocyte Count; D019272:Leukocyte Elastase; D007962:Leukocytes / Q000166:cytology; D009504:Neutrophils; D010196:Pancreatic Elastase / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits
D007375:Interleukin-1; D016209:Interleukin-8; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D003094:Collagen; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D017364:Collagenases; D018093:Gelatinases; D015232:Dinoprostone