SECRETION OF INTERLEUKIN-6 BY HUMAN ENDOMETRIOTIC CELLS AND REGULATION BY PROINFLAMMATORY CYTOKINES AND SEX STEROIDS

Endometriosis is generally associated with an immunoinflammatory proce ss that takes place in the peritoneal cavity of patients, Interleukin (IL)-6, a multifunctional cytokine involved in numerous immunological and proliferative processes, has been found at high concentrations in the peritoneal fluid of endometriosis patients. The purpose of this st udy was to investigate the ability of endometriotic cells to produce I L-6 and to assess the regulation of its secretion by proinflammatory c ytokines and sex steroids. Cultures of human endometriotic cells were exposed to different concentrations of cytokines and sex steroid hormo nes for varying periods of time, IL-6 secretion was measured using an enzyme-linked immunosorbent assay. Endometriotic cells spontaneously r eleased IL-6 in culture. IL-1 beta and tumour necrosis factor (TNF)-al pha (0.1-100.0 ng/ml) potentiated IL-6 secretion in a time- and dose-d ependent manner. Interferon-gamma (0.4-400 ng/ml) induced a dose-relat ed increase in IL-6 secretion and showed a synergistic effect on that secretion in combination with TNF-alpha (10 ng/ml). Either spontaneous or cytokine-induced IL-6 secretion was inhibited by progesterone (10( -8)-10(-5) M) and danazol (10(-6) M), whereas oestradiol (10(-8)-10(-5 ) M) had a limited inhibitory effect, The antiprogestin RU486 (10(-8)- 10(-4) M) antagonized the inhibitory effects of progesterone and danaz ol, but showed agonist action when used alone. These findings indicate that endometriotic tissue may actively contribute to the biological c hanges observed in the peritoneal fluid of endometriosis patients, The y also provide new insights into the mechanisms of action of progester one and those of danazol and RU486 used in the treatment of endometrio sis.