Role of IL-18 in pathogenesis of endometriosis

BACKGROUND: Endometriosis is a complex disease associated with a wide range of immune responses, including pain, adhesion, exudation of peritoneal ¯uid, elevation of cytokine levels and generation of autoantibodies. Interleukin (IL)-18 is a strong pleiotropic cytokine known to be involved in various immune diseases. The aim of this study is to elucidate the role of IL-18 in the pathogenesis of endometriosis. METHODS: IL-18 and IL-1b concentrations were measured in the peritoneal ¯uid and sera of 39 endometriosis patients and 15 control women. Expression of IL-18 and IL-18 receptor a-chain (IL-18Ra) was analysed in endometriotic tissues immuno-histochemically. The effects of IL-18 on cyclooxygenase (COX)-II gene expression were analysed in peritoneal ¯uid monocytes and endometriotic cells of endometriosis patients. RESULTS: IL-18 concentrations in the peritoneal ¯uid of endometriosis patients averaged 592.57 6 108.27 pg/ml, signi®cantly higher than 260.50 6 55.88 pg/ml in non-endometriotic samples. IL-18 concentrations in the serum did not differ signi®cantly between endometriosis and control patients. Similarly, no signi®cant differences were observed in IL-1b concentrations in either the peritoneal ¯uid or the serum. IL-18 and IL-18Ra were expressed in endometriotic tissues. IL-18Ra expression was also observed in cells in®ltrating into the in¯ammatory area of the endometriosis patients. COX-II was induced in peritoneal ¯uid monocytes and in endometriotic cells in response to IL-18 stimulation. CONCLUSIONS: The elevation of IL-18 in the peritoneal ¯uid of endometriosis patients and the induction of COX-II in peritoneal monocytes by IL-18 suggest that IL-18 plays a pathogenic role in endometriosis.