Analysis of the cytokine interaction among interleukin-1beta, interleukin-8, and interleukin-1 receptor antagonist in the rabbit ovulatory process.
OBJECTIVE
To elucidate the regulation and involvement of interleukin (IL)-1beta, IL-8, and IL-1 receptor antagonist in the hCG-induced rabbit ovulatory process.


METHODS
Randomized, controlled animal study.


METHODS
University research laboratory.


METHODS
Mature female New Zealand white rabbits.


METHODS
After i.v. administration of 100 IU of hCG to rabbits, ovarian levels of IL-1beta. IL-8, and IL-1 receptor antagonist were determined at indicated times by ELISA. Anti IL-1beta, anti-lL-8, or anti-IL-1 receptor antagonist antiserum was given i.v. 30 minutes before hCG injection.


METHODS
Effects of each antiserum on the levels of the other cytokines and neutrophil accumulation, assessed by myeloperoxidase activity, were determined. Ovulation rate (rate of ruptured follicles) was also evaluated.


RESULTS
The maximal level of IL-8 was detected at 4 hours. which preceded that of IL-1beta and IL-1 receptor antagonist, detected at 6 hours after hCG injection. Administration of anti-IL-1beta antiserum resulted in a statistically significant reduction of the peak levels of IL-8 and IL-1 receptor antagonist. Administration of anti-IL-8 antiserum reduced the accumulation of IL-1beta and IL-1 receptor antagonist. Anti-IL-1 receptor antagonist antiserum significantly augmented the accumulation of IL-1beta and IL-8. Myeloperoxidase activity was reduced by anti-IL-8 antiserum. Anti-IL-1beta and anti-lL-8 antiserum reduced the hCG-induced ovulation rate, but a synergistic effect was not evident when these antisera were injected simultaneously. Anti-IL-1 receptor antagonist antiserum had no apparent effect on ovulatory efficiency.


CONCLUSIONS
IL-1beta, IL-8, and IL-1 receptor antagonist may affect the accumulation of related cytokines in ovaries and may be involved in ovulation.
Ujioka
T
T
Department of Obstetrics and Gynecology, Kumamoto University School of Medicine, Honjo, Japan.
Matsukawa
A
A
Tanaka
N
N
Matsuura
K
K
Yoshinaga
M
M
Okamura
H
H
D000818:Animals; D006063:Chorionic Gonadotropin / Q000627:therapeutic use; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010060:Ovulation / Q000502:physiology*; D010062:Ovulation Induction / Q000379:methods; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*
D006063:Chorionic Gonadotropin; D007375:Interleukin-1; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D009195:Peroxidase