title: Indoleamine 2,3-dioxygenase in the pathogenesis of tuberculous pleurisy.
abstract: BACKGROUND
  Pleural fluid is a frequent manifestation in pulmonary diseases, such as lung cancer and infectious diseases, including pulmonary tuberculosis (TB). The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses tryptophan through the kynurenine pathway, and is considered a crucial immunoregulatory molecule mediating immune tolerance. Recent studies have shown IDO activity to be a novel prognostic factor not only in cancer patients but also in those with infectious diseases, including pneumonia and pulmonary TB. However, no studies have measured and determined the clinical significance of IDO activity in pleural fluid.
  
  
  METHODS
  We enrolled 92 patients, including 34 with tuberculous pleurisy (TBP), 36 with malignant pleuritis and 15 with parapneumonic effusions. IDO activity was evaluated using liquid chromatography/electrospray ionisation tandem mass spectrometry, and was estimated by calculating kynurenine-to-tryptophan ratio.
  
  
  RESULTS
  Pleural fluid from patients with TBP had significantly higher kynurenine concentrations and significantly lower tryptophan concentrations, resulting in significantly higher IDO activity compared with pleural effusion or serum from non-tuberculous pleuritis (all P < 0.001). Pleural tissue from TBP showed enhanced IDO expression in epithelioid granuloma regions by immunohistochemistry.
  
  
  CONCLUSIONS
  These results suggest that IDO is strongly involved in the pathogenesis of TBP.
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Hamamatsu, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Miwa
authors.forename: T
authors.initials: T
authors.lastname: Akamatsu
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Fujie
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: N
authors.initials: N
authors.lastname: Inui
authors.forename: H
authors.initials: H
authors.lastname: Hayakawa
authors.forename: K
authors.initials: K
authors.lastname: Chida
authors.forename: T
authors.initials: T
authors.lastname: Suda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000032:analysis*; D007737:Kynurenine / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000201:enzymology*; D011446:Prospective Studies; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014364:Tryptophan / Q000032:analysis; D014396:Tuberculosis, Pleural / Q000201:enzymology*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan