Association of interleukin-6 and estradiol with hepatocyte growth factor in peritoneal fluid of women with endometriosis

BACKGROUND: Different cytokines and ovarian steroid hormones have been reported to regulate the growth and maintenance of endometriosis. We determined the relationship between peritoneal fluid concentrations of interleukin-6, ovarian steroids and hepatocyte growth factor in different revised American Fertility Society (AFS) staging and morphologic appearances of endometriosis. METHODS: Peritoneal fluid was collected from 30 women with endometriosis and 20 women without endometriosis during laparoscopy, and hepatocyte growth factor, interleukin(IL)-6 and ovarian steroids were measured in peritoneal fluid. The concentrations of hepatocyte growth factor and IL-6 in peritoneal fluid were measured by ELISA, and that of estradiol and progesterone by using the immulyze-enzyme amplified luminescence system. Changes in peritoneal fluid concentrations of hepatocyte growth factor, IL-6, estradiol and progesterone in different stages and morphologic appearances of endometriosis were examined to demonstrate their differences in early and advanced endometriosis. RESULTS: Peritoneal fluid levels of hepatocyte growth factor in women with stage I-II endometriosis were significantly higher than in both women with stage III-IV endometriosis and without endometriosis. A similar significant increase in stage I-II endometriosis was also observed for IL-6 and estradiol. When we divided the women according to different morphologic appearances of endometriosis, we found significantly higher concentrations of hepatocyte growth factor (HGF), IL-6, estradiol and progesterone in women containing red lesions compared with other pigments or without endometriosis. A positive correlation was observed between peritoneal fluid levels of IL-6 and hepatocyte growth factor only but not between other markers. Although estradiol levels in peritoneal fluid showed an increased tendency to elevate in the proliferative phase of endometriosis women, hepatocyte growth factor and progesterone displayed higher concentrations in the secretory phase of the menstrual cycle. After adjusting different variables in peritoneal fluid, multiple analysis of covariance indicated that hepatocyte growth factor levels in peritoneal fluid were independently involved in the red morphologic activity of endometriosis. CONCLUSIONS: Early staging and red color appearance of endometriosis are associated with the elevation in peritoneal fluid concentrations of hepatocyte growth factor, IL-6 and estradiol, demonstrating the combined effect of these cytokines and ovarian steroids in the production of hepatocyte growth factor from endometrial tissues in active endometriosis.