Analysis of the cytokine interaction among interleukin-1β, interleukin-8, and interleukin-1 receptor antagonist in the rabbit ovulatory process

Abstract

Objective: To elucidate the regulation and involvement of interleukin (IL)-1β, IL-8, and IL-1 receptor antagonist in the hCG-induced rabbit ovulatory process. Design: Randomized, controlled animal study. Setting: University research laboratory. Animal(s): Mature female New Zealand white rabbits. Intervention(s): After IV administration of 100 IU of hCG to rabbits, ovarian levels of IL-1β, IL-8, and IL-1 receptor antagonist were determined at indicated times by ELISA. Anti–IL-1β, anti–IL-8, or anti–IL-1 receptor antagonist antiserum was given IV 30 minutes before hCG injection. Main Outcome Measure(s): 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. Result(s): The maximal level of IL-8 was detected at 4 hours, which preceded that of IL-1β and IL-1 receptor antagonist, detected at 6 hours after hCG injection. Administration of anti–IL-1β 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-1β and IL-1 receptor antagonist. Anti–IL-1 receptor antagonist antiserum significantly augmented the accumulation of IL-1β and IL-8. Myeloperoxidase activity was reduced by anti–IL-8 antiserum. Anti–IL-1β 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 antagonist antiserum had no apparent effect on ovulatory efficiency. Conclusion(s): IL-1β, IL-8, and IL-1 receptor antagonist may affect the accumulation of related cytokines in ovaries and may be involved in ovulation.