title: Interleukin 12, interleukin 18, and tumor necrosis factor alpha release by alveolar macrophages: acute and chronic hypersensitivity pneumonitis.
abstract: BACKGROUND
  Hypersensitivity pneumonitis (HP) is characterized by a granulomatous inflammation and may show various forms of clinical presentation, such as the acute, subacute, and chronic forms. The TH1-associated cytokines interleukin (IL) 12 and IL-18 and tumor necrosis factor alpha (TNF-alpha) may be involved in the pathogenesis of both the acute and chronic forms of HP.
  
  
  OBJECTIVE
  To compare the release of IL-12, IL-18, and TNF-alpha from bronchoalveolar lavage (BAL) macrophages in these 2 forms of HP.
  
  
  METHODS
  Patients underwent BAL 0 to 6 days after the last antigen exposure. Alveolar macrophages (AMs) from BAL in 6 patients with acute HP, 16 with chronic HP, and 11 controls were cultured for 24 hours. Cytokines in the culture supernatants were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The production of IL-12, IL-18, and TNF-alpha by AMs was increased in patients with both acute and chronic forms in either the absence or presence of lipopolysaccharide compared with controls. The levels of IL-12, IL-18, and TNF-alpha showed no difference between patients with acute and chronic HP. The spontaneous production of IL-12, IL-18, and TNF-alpha did not correlate with the CD4/CD8 ratio in BAL. The spontaneous and lipopolysaccharide-stimulated release of IL-12 showed a positive correlation with the percentage of lymphocytes (r = .470, P = .03; r = .496, P = .02; respectively) in BAL.
  
  
  CONCLUSIONS
  This study demonstrates that an increased release of IL-12, IL-18, and TNF-alpha by AMs is associated with both the acute and chronic forms of HP.
authors.affiliation: Department of Pneumology and Allergology, Ruhrlandklinik, Medical Faculty, University of Duisburg-Essen, Germany.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Ye
authors.forename: Shinobu
authors.initials: S
authors.lastname: Nakamura
authors.forename: Rafael
authors.initials: R
authors.lastname: Sarria
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
authors.forename: Josune
authors.initials: J
authors.lastname: Guzman
mesh_terms: D000328:Adult; D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012015:Reference Standards; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12