title: Serum and peritoneal interleukin-33 levels are elevated in deeply infiltrating endometriosis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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, 8.0-104.9) than in endometriosis-free women (median, 61.3 pg/ml; range, 7.5-526.0; P = 0.022) or in women affected by superficial endometriosis (median, 36.8 pg/ml; range, 7.5-179.0; P < 0.001). Peritoneal IL-33 was higher in DIE than in endometriosis-free women (median, 642.0 pg/ml; range, 25.9-3350.6 versus median, 194.2 pg/ml; range, 12.7-1818.2, 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gynecology Obstetrics II and Reproductive Medicine, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, AP-HP, Hôpital Cochin, 75679 Paris, France. pietro.santulli@inserm.fr
authors.forename: Pietro
authors.initials: P
authors.lastname: Santulli
authors.forename: Bruno
authors.initials: B
authors.lastname: Borghese
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chouzenoux
authors.forename: Daniel
authors.initials: D
authors.lastname: Vaiman
authors.forename: Didier
authors.initials: D
authors.lastname: Borderie
authors.forename: Isabelle
authors.initials: I
authors.lastname: Streuli
authors.forename: François
authors.initials: F
authors.lastname: Goffinet
authors.forename: Dominique
authors.initials: D
authors.lastname: de Ziegler
authors.forename: Bernard
authors.initials: B
authors.lastname: Weill
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
authors.forename: Charles
authors.initials: C
authors.lastname: Chapron
mesh_terms: D000328:Adult; D001202:Ascitic Fluid / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000097:blood* / Q000378:metabolism*; D056627:Peritoneal Fibrosis / Q000378:metabolism*; D010537:Peritoneum / Q000378:metabolism*; D011446:Prospective Studies
chemical_list: D016207:Cytokines; C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins