PROBLEM: Interleukin-18 (IL-18) strongly induces interferon-gamma production and is produced not only by types of immune cells but also by types of non-immune cells. Ovulation is thought to be an inflammation-like reaction in which many pro-inflammatory cytokines are involved. We investigated whether IL-18 is involved in the functions of ovary.
METHOD OF STUDY: The 4-week-old immature female mice were examined for IL-18 and IL-18 receptor (IL-18R) expression on their ovaries under stimulation with pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) by immunohistochemical staining, Western blotting and reverse transcript-polymerase chain reaction. The IL-18R was blocked by the injection of anti-IL-18R monoclonal antibody to immature mice during PMSG-hCG stimulation, and the number of ovulated ova was counted.
RESULTS: The expression of both proteins and mRNA of IL-18 and IL-18R were very low in immature ovaries before stimulation, but after PMSG injection both IL-18 and IL-18R increased dramatically in theca cells and reached a maximum level at the peri-ovulatory phase then slightly lowered, but still kept a high level during the luteal phase in the corpus luteum.
The treatment of IL-18R monoclonal antibody to the mice during ovarian stimulation reduced the number of ovulated ova and inhibited the expansion of cumulus cells surrounding the ovum.
CONCLUSION: IL-18 and IL-18R play roles in various kinds of function of ovary.