title: Tumor necrosis factor-alpha in a porcine bronchial model of obliterative bronchiolitis.
abstract: BACKGROUND
  In posttransplant obliterative bronchiolitis (OB), the major pathologic features are inflammation, epithelial cell injury, fibrosis, and obliteration of the small airways. Tumor necrosis factor (TNF)-alpha is a cytokine known to mediate and augment the inflammatory reaction and to enhance fibroblast proliferation. We assessed the role of TNF-alpha in the development of OB in our heterotopic porcine bronchial transplantation model.
  
  
  METHODS
  Three groups were formed: autografts, nontreated allografts, and allografts treated with preoperative anti-TNF-alpha monoclonal antibody (infliximab) infusion. The implants were harvested on days 2, 4, 7, 11, 14, 21, and 28 for histologic and immunohistochemical analysis.
  
  
  RESULTS
  TNF-alpha inhibition reduced inflammation, rate of epithelial loss, fibrosis, and obliteration early in the development of OB. In the epithelium, the numbers of TNF-alpha-positive epithelial and inflammatory cells and macrophages were significantly lower in treated than in nontreated allografts on day 4; furthermore, in the epithelium and in the bronchial wall, invasion of CD8+ lymphocytes was significantly decreased during the first week.
  
  
  CONCLUSIONS
  These results indicate that TNF-alpha promotes the development of OB, and inhibition of TNF-alpha may prove beneficial in a clinical setting.
authors.affiliation: Department of Surgery, Helsinki University Hospital, Helsinki, Finland. hanni.alho@helsinki.fi.
authors.forename: Hanni S
authors.initials: HS
authors.lastname: Alho
authors.forename: Paula K
authors.initials: PK
authors.lastname: Maasilta
authors.forename: Ari L J
authors.initials: AL
authors.lastname: Harjula
authors.forename: Pekka
authors.initials: P
authors.lastname: Hämmäinen
authors.forename: Jukka
authors.initials: J
authors.lastname: Salminen
authors.forename: Ulla-Stina
authors.initials: US
authors.lastname: Salminen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001980:Bronchi / Q000473:pathology / Q000637:transplantation*; D001989:Bronchiolitis Obliterans / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D000069285:Infliximab; D011183:Postoperative Complications / Q000473:pathology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab