ANALYSIS OF THE CYTOKINE INTERACTION AMONG INTERLEUKIN-L-BETA, INTERLEUKIN-8, AND INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE RABBIT OVULATORYPROCESS

Objective: To elucidate the regulation and involvement of interleukin (IL)-1 beta, IL-8, and IL-1 receptor antagonist in the hCG-induced rab bit ovulatory process. Design: Randomized, controlled animal study. Se tting: University research laboratory. Animal(s): Mature female New Ze aland white rabbits. Intervention(s): After IV administration of 100 I U of hCG to rabbits, ovarian levels of IL-1 beta, IL-8, and IL-1 recep tor antagonist were determined at indicated times by ELISA. Anti-IL-1 beta, anti-IL-8, or anti-IL-1 receptor antagonist antiserum was given IV 30 minutes before hCG injection. Main Outcome Measure(s): Effects o f each antiserum oil the levels of the other cytokines and neutrophil accumulation, assessed by myeloperoxidase activity, were determined. O vulation rate (rate of ruptured follicles) was also evaluated. Result( s): The maximal level of IL-8 was detected at 4 hours, which preceded that of IL-1 beta and IL-1 receptor antagonist, detected at 6 hours af ter hCG injection. Administration of anti-IL-1 beta antiserum resulted in a statistically significant reduction of the peak levels of IL-8 a nd IL-1 receptor antagonist. Administration of anti-IL-8 antiserum red uced the accumulation of IL-1 beta and IL-1 receptor antagonist. Anti- IL-1 receptor antagonist antiserum significantly augmented the accumul ation of IL-1 beta and IL-8. Myeloperoxidase activity was reduced by a nti-IL-8 antiserum. Anti-IL-1 beta and anti-IL-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 a ntagonist antiserum had no apparent effect on ovulatory efficiency. Co nclusion(s): IL-1 beta, IL-8, and IL-1 receptor antagonist may affect the accumulation of related cytokines in ovaries and may be involved i n ovulation. (Fertil Steril(R) 1998;70:759-65. (C) 1998 by American So ciety for Reproductive Medicine.).