title: Profibrotic interleukin-33 is correlated with uterine leiomyoma tumour burden.
abstract: OBJECTIVE
  Are interleukin-33 (IL-33) serum levels higher in women with uterine leiomyoma compared with controls without leiomyoma?
  
  
  CONCLUSIONS
  Serum IL-33 is elevated in women with uterine leiomyoma and correlated with features of uterine leiomyoma tumour burden, namely fibroid number, size and weight.
  
  
  BACKGROUND
  Uterine leiomyomas are the most common benign tumours in premenopausal women associated with major tissue fibrosis. IL-33 is a cytokine involved in fibrotic disorders. The potential role of IL-33 in leiomyoma has not been reported before.
  
  
  METHODS
  This is a prospective laboratory study conducted in a tertiary-care university hospital between January 2005 and December 2010. We investigated non-pregnant, 42-year-old patients (n = 151) during surgery for a benign gynaecological condition.
  
  
  METHODS
  After complete surgical exploration of the abdominopelvic cavity, 59 women with histologically proved uterine leiomyoma and 92 leiomyoma-free control women were enrolled. Women with endometriosis or past history of ovarian malignancy and borderline tumours were not included. The control group included women with benign ovarian cysts, paratubal cysts or tubal defects without any evidence of uterine leiomyoma. For each patient, a structured questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. Serum samples were obtained in the month preceding the surgical procedures according to the menstrual phase or hormonal therapy. IL-33 was measured in sera by enzyme-linked immunosorbent assay, and correlation of IL-33 concentration with the extent and severity of the disease was investigated.
  
  
  RESULTS
  IL-33 was detected in 32 (54.2%) women with leiomyoma and 18 (19.6%) controls (P < 0.001). Serum IL-33 was higher in women with leiomyoma (median, 140.1 pg/ml; range, 7.5-2247.7) than in controls (median, 27.8 pg/ml; range, 7.5-71.6; P = 0.002). We found positive correlations between serum IL-33 concentration and leiomyoma features, such as fibroid weight (r = 0.630; P = 0.001) and size (r = 0.511; P = 0.018) and the number of fibroids (r = 0.503; P = 0.003).
  
  
  CONCLUSIONS
  There was a possible selection bias due to inclusion of only surgical patients. Therefore our control group consisted of women who underwent surgery for benign gynaecological conditions. This may lead to biases stemming from the fact that certain of these conditions, such as tubal infertility or ovarian cysts, might be associated with altered serum IL-33 levels.
  
  
  CONCLUSIONS
  We demonstrate for the first time that elevated serum IL-33 levels are associated with the existence of uterine leiomyoma. However, even if an association does not constitute proof of cause and effect, investigating the mechanisms that underlie fibrogenesis associated with leiomyomas is a step towards understanding this enigmatic disease. This study opens the doors to future, more mechanistics studies to establish the exact role of IL-33 in uterine leiomyomas pathogenesis.
  
  
  BACKGROUND
  No funding, no conflict of interest.
authors.affiliation: Department of Gynecology Obstetrics II and Reproductive Medicine, Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, AP-HP, Hôpital Cochin, 75679 Paris, France. pietro.santulli@cch.aphp.fr
authors.forename: Pietro
authors.initials: P
authors.lastname: Santulli
authors.forename: Marc
authors.initials: M
authors.lastname: Even
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chouzenoux
authors.forename: Anne-Elodie
authors.initials: AE
authors.lastname: Millischer
authors.forename: Bruno
authors.initials: B
authors.lastname: Borghese
authors.forename: Dominique
authors.initials: D
authors.lastname: de Ziegler
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
authors.forename: Charles
authors.initials: C
authors.lastname: Chapron
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000097:blood*; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology; D047368:Tumor Burden; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins
keywords: fibroids; fibrosis; interleukin; interleukin-33; pathogenesis