Differential expression of T-helper cytokines in the peritoneal fluid of women with normal ovarian cycle compared with women with chronic anovulation.

BACKGROUND

Estrogen and progesterone immunoregulate the genital environment by expression of cytokines and growth factors.

OBJECTIVE

To investigate the pattern of expression of T-helper cytokines during the ovarian cycle compared with women with chronic anovulation resistant to clomiphene citrate.

HYPOTHESIS

Expression of T-helper cytokines in women with chronic anovulation may be different from the pattern in women with a normal ovarian cycle.

METHODS

We evaluated 31 infertile women having laparoscopy for evaluation of tubal patency and evidence of ovulation in two groups during (a) the luteal phase (17 women) and (b) the follicular phase (14 women). A third group was composed of 14 women with polycystic ovarian syndrome, but they were resistant to clomiphene citrate for induction of ovulation and had laparoscopic ovarian cautery. Peritoneal fluid was collected during laparoscopy. Estimation of T-helper cytokine interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, IL-4 and IL-6 in serum, peritoneal fluid and culture of the peritoneal mononuclear cells was performed by ELISA. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, estradiol and progesterone were evaluated by the Vidas Parametric System.

RESULTS

The LH : FSH ratio was significantly higher in the women with polycystic ovaries than in the ovulatory groups. IL-2 and IFN-gamma were more highly expressed in the follicular phase but the T-helper 2 cytokines IL-4 and IL-6 predominated in the luteal phase, serum, peritoneal fluid and culture of the peritoneal mononuclear cells. From the follicular to the mid-luteal phase, IL-6 increased three to fivefold in the serum and peritoneal fluid, but there was low expression with anovulation.

CONCLUSIONS

The peritoneal fluid levels of IL-4 and IL-6 are higher in the luteal phase. Low IL-6 levels in chronic anovulation may be a marker of resistance to clomiphene citrate.