Tumor necrosis factor-alpha in a porcine bronchial model of obliterative bronchiolitis

Transplantation. 2003 Aug 15;76(3):516-23. doi: 10.1097/01.TP.0000074700.30536.76.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Bronchi / pathology
  • Bronchi / transplantation*
  • Bronchiolitis Obliterans / pathology*
  • CD8-Positive T-Lymphocytes / pathology
  • Immunohistochemistry
  • Inflammation / pathology
  • Infliximab
  • Postoperative Complications / pathology
  • Swine
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / physiology*


  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Infliximab