Peritoneal environment and angiogenesis in the pathophysiology of endometriosis
We investigated peritoneal fluid levels of the cytokines, interleukin-8 (IL-8), IL-12, IL-11 and IL-14 in women with and without endometriosis to identify any possible role for these molecules in the pathophysiology of the disease. In addition, in vitro culture studies were carried out investigating the effects of IL-8, anti-IL-8, IL-12 and PUFAs on endometrial cell proliferation at varying concentrations. The production of IL-8 by endometrial cells under the influence of PUFAs was also studied. We found that IL-8 was significantly increased in the peritoneal fluid of women with endometriosis especially in its early stages. Levels of IL-12, IL-11 and IL-4 did not show any correlation to the presence or the stage of endometriosis. While IL-8 stimulated, IL-12 did not significantly influence in vitro endometrial cell survival at concentrations used in our studies, while the effect of a IL-8 varied according to the dose used. Increased n-3 PUFA exposure significantly suppressed the in vitro survival of endometrial cells from women with and without endometriosis. Endometrial cells from women with endometriosis produced higher levels of IL-8 especially in the presence of high n-3 PUFAs in the culture environment. Our findings suggest that peritoneal angiogenesis especially under the influence of IL-8 may play a decisive role in the development of endometriosis. PUFAs may influence the viability of endometrial fragments shed into the cavity via retrograde menstruation. We speculate that manipulation of dietary intake of PUFAs could prove to be a way forward in the management of endometriosis.