title: Dienogest improves human leucocyte antigen-DR underexpression and reduces tumour necrosis factor-α production in peritoneal fluid cells from women with endometriosis.
abstract: OBJECTIVE
  To determine the immunological effect of dienogest (DNG), an oral anti-endometriosis drug, on peritoneal fluid (PF) macrophages collected from women with endometriosis. Although it has been suggested that DNG has direct effects on endometriotic cells, including decreased cell proliferation and decreased anti-inflammatory cytokine production, the effects of DNG on PF cells are unclear.
  
  
  METHODS
  The effects of DNG on PF cells from 34 women with endometriosis and 22 women without endometriosis (controls) were investigated. Expression of human leucocyte antigen (HLA)-DR in PF macrophages, obtained from the peritoneal cavity during laparoscopic surgery, was determined by flow cytometry. HLA-DR expression was measured again after PF cells had been cultured for 72 h in a humidified atmosphere at 37 °C in 5% CO₂-95% air with or without DNG. After 72 h of incubation, the concentration of pro-inflammatory tumour necrosis factor (TNF)-α in the media was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  HLA-DR expression was lower in PF macrophages from women with endometriosis compared with controls. However, after DNG treatment, HLA-DR expression in PF macrophages from women with endometriosis was increased to the same level as in controls. The TNF-α concentration in the media was decreased by DNG.
  
  
  CONCLUSIONS
  DNG can restore the antigen-presenting ability of PF macrophages by increased HLA-DR expression, and may have an anti-inflammatory effect on PF macrophages in women with endometriosis.
authors.affiliation: Department of Obstetrics and Gynaecology, Kochi Medical School, Nankoku, Kochi, Japan. Electronic address: maedan@kochi-u.ac.jp.
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Obstetrics and Gynaecology, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Izumiya
authors.affiliation: Department of Obstetrics and Gynaecology, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: Department of Obstetrics and Gynaecology, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Matsushima
authors.affiliation: Development Research, Mochida Pharmaceutical Co., Ltd, Gotemba, Shizuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Mita
authors.affiliation: Development Research, Mochida Pharmaceutical Co., Ltd, Gotemba, Shizuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Department of Obstetrics and Gynaecology, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fukaya
mesh_terms: D000328:Adult; D001202:Ascitic Fluid / Q000166:cytology; D002478:Cells, Cultured; D004715:Endometriosis / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis*; D006727:Hormone Antagonists / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D010532:Peritoneal Diseases / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D006684:HLA-DR Antigens; D006727:Hormone Antagonists; D014409:Tumor Necrosis Factor-alpha; C023635:dienogest; D009277:Nandrolone
keywords: Dienogest; Endometriosis; Human leucocyte antigen-DR; Peritoneal fluid cells; Tumour necrosis factor-α