Endometriosis: Secretion of interleukin-6 by human endometriotic cells and regulation by proinflammatory cytokines and sex steroids

Endometriosis is generally associated with an immuno-inflammatoryprocess that takes place in the peritoneal cavity of patients.Interleukin (IL)-6, a multifunctional cytokine involved in numerousimmunological and prolifer-ative processes, has been found athigh concentrations in the peritoneal fluid of endometriosispatients. The purpose of this study was to investigate the abilityof endometriotic cells to produce IL-6 and to assess the regulationof its secretion by proinflammatory cytokines and sex steroids.Cultures of human endometriotic cells were exposed to differentconcentrations of cytokines and sex steroid hormones for varyingperiods of time. IL-6 secretion was measured using an enzyme-linkedimmunosorbent assay. Endometriotic cells spontaneously releasedIL-6 in culture. IL-1 and tumour necrosis factor (TNF)- (0.1–100.0ng/ ml) potentiated IL-6 secretion in a time- and dose-dependentmanner. Interferon- (0.4–400 ng/ml) induced a dose-relatedincrease in IL-6 secretion and showed a synergjstic effect onthat secretion in combination with TNF- (10 ng/ ml). Eitherspontaneous or cytokine-induced IL-6 secretion was inhibitedby progesterone (10^–8–10^–5 M) and danazol(10^–6 M), whereas oestradiol (10^–8–10^–5M) had a limited inhibitory effect. The antiprogestin RU486(l0^–8–10^–4 M) antagonized the inhibitory effectsof progesterone and danazol, but showed agonist action whenused alone. These findings indicate that endometriotic tissuemay actively contribute to the biological changes observed inthe peritoneal fluid of endometriosis patients. They also providenew insights into the mechanisms of action of progesterone andthose of danazol and RU486 used in the treatment of endometriosis.