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

Endometriosis, an oestrogen-dependent disorder affecting women of reproductive age, is associated with active angiogenesis and an increased recruitment of leukocyte into the peritoneal cavity where the implants often develop. The role of oestrogens in the development of endometriosis has been clearly established, but the biochemical mechanisms of their action are still not clearly elucidated. The present study shows that interleukin-1 (IL-1) induces interleukin-8 (IL-8) secretion by endometriotic cells and that oestradiol enhances endometriotic cell responsiveness to IL-1. In contrast, no significant cell responsiveness to progesterone either alone in the culture medium or in combination with oestradiol was noted. Positive immunostaining for IL-8 was observed throughout endometriotic tissue, and no perceptible difference in the intensity of staining regarding the menstrual cycle phase was observed. Together with the in-vitro data, this suggests that IL-8 expression in endometriotic tissue is not subject to cyclic variation. Furthermore, this study provides evidence that oestradiol indirectly up-regulates the expression by ectopic endometrial cells of IL-8, a cytokine endowed with neutrophil chemotactic and angiogenic properties. This may contribute to peritoneal leukocyte recruitment and to the growth of endometriotic implants, and may be a new mechanism for oestradiol action in endometriosis.