Serum and peritoneal interleukin-33 levels are elevated in deeply infiltrating endometriosis

Interleukin 33 (IL-33) is a cytokine involved in fibrotic disorders. We have analyzed IL-33 levels in the sera and peritoneal fluids of women with various forms of endometriosis and investigated the correlation with disease activity. We conducted a prospective laboratory study in a tertiary-care university hospital between January 2005 and December 2010. Five hundred and ten women with histologically proven endometriosis and 132 endometriosis-free controls were enrolled in this study. Complete surgical exploration of the abdominopelvic cavity was performed in each patient. Blood samples and peritoneal fluids were obtained before and during surgical procedures, respectively. IL-33 was measured by an enzyme-linked immunosorbent assay in sera and peritoneal fluids, and the concentrations correlated with the extent and the severity of endometriotic lesions. IL-33 was detectable in 23.1 of serum samples from all 642 women studied and 75.0 of peritoneal fluid samples studied (44 women with endometriosis and 36 controls). Serum IL-33 was higher in deeply infiltrating endometriosis (DIE) (median, 104.9 pg/ml; range, 8.0104.9) than in endometriosis-free women (median, 61.3 pg/ml; range, 7.5526.0; P 0.022) or in women affected by superficial endometriosis (median, 36.8 pg/ml; range, 7.5179.0; P 0.001). Peritoneal IL-33 was higher in DIE than in endometriosis-free women (median, 642.0 pg/ml; range, 25.93350.6 versus median, 194.2 pg/ml; range, 12.71818.2, respectively; P 0.003). We found positive correlations between serum IL-33 concentration and intensity of dysmenorrhea (r 0.174; P 0.028) and gastrointestinal symptoms (r 0.199; P 0.027), total number of DIE lesions (r 0.224; P 0.016) and the worst DIE lesion (r 0.299; P 0.001). In spite of the number of samples with undetectable levels, serum IL-33 is abnormally elevated in women with endometriosis and principally in DIE. Elevated serum IL-33 is correlated with the intensity of preoperative painful symptoms, and with the extent and severity of the DIE. IL-33 may be considered as a novel cytokine involved in the pathogenesis of DIE.