Ectopic endometrial cells express high concentrations of interleukin (IL)-8 in vivo regardless of the menstrual cycle phase and respond to oestradiolby up-regulating IL-1-induced IL-8 expression in vitro

Endometriosis, an oestrogen-dependent disorder affecting women of reproduct ive age, is associated with active angiogenesis and an increased recruitmen t of leukocyte into the peritoneal cavity where the implants often develop. The role of oestrogens in the development of endometriosis has been clearl y established, but the biochemical mechanisms of their action are still not clearly elucidated. The present study shows that interleukin-1 (IL-1) indu ces interleukin-8 (IL-8) secretion by endometriotic cells and that oestradi ol enhances endometriotic cell responsiveness to IL-I. In contrast, no sign ificant cell responsiveness to progesterone either alone in the culture med ium or in combination with oestradiol was noted. Positive immunostaining fo r IL-8 was observed throughout endometriotic tissue, and no perceptible dif ference in the intensity of staining regarding the menstrual cycle phase wa s observed. Together with the in-vitro data, this suggests that IL-8 expres sion in endometriotic tissue is not subject to cyclic variation. Furthermor e, this study provides evidence that oestradiol indirectly up-regulates the expression by ectopic endometrial cells of IL-8, a cytokine endowed with n eutrophil chemotactic and angiogenic properties. This may contribute to per itoneal leukocyte recruitment and to the growth of endometriotic implants, and may be a new mechanism for oestradiol action in endometriosis.