Cytokines' role, especially G-CSF and IL-6, on human ovarian function and its clinical application

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We have revealed the effects of cytokines, especially G-CSF and IL-6 on ovarian function as follows.1) Cyclic changes of cytokines during the normal menstrual cycleThe cyclic changes of the cytokines▲(TNF-α, IL-1β, IL-6, GM-CSF, M-CSF) in serum that were already reported to be involved in the mechanism of ovulation and G-CSF were measured during the normal menstrual cycle. Only G-CSF showed a significant increase a few days before ovulation. Although it was not significant, IL-6 showed an increase during the late luteal phase.2) Cyclic changes of IL-6 at the human follicular wall and its relation to the luteal regressionThe expression of IL-6 mRNA at the human follicular wall increased significantly in the regressing corpus luteum. Moreover, increased IL-6 protein and receptor were observed in the follicular wall of the late luteal phase. These results will contribute to elucidate the mechanism of luteal insufficiency.3) Clinical trial to use G-CSF as a supportive drug to ovulation inductionThe following clinical trials were conducted to induce ovulation in the patients of luteinized unruptured follicle (LUF). The patients who showed LUF at the last Clomiphene-hCG cycle participated in this clinical trial. Ovulation induction using Clomiphene-hCG was performed as the last cycle. In addition, G-CSF 100 μg was administered 24-48 hours before hCG. The ovulation was successfully induced at the rate of 87.1% (54/62). Since the ovulation rate of the patients before this clinical trial was 53.5 %, the rate is significantly high (p<0.01).Our results established a new method to induce ovulation using G-CSF.