Tumor necrosis factor-alpha in a porcine bronchial model of obliterative bronchiolitis.
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.
Alho
Hanni S
HS
Department of Surgery, Helsinki University Hospital, Helsinki, Finland. hanni.alho@helsinki.fi.
Maasilta
Paula K
PK
Harjula
Ari L J
AL
Hämmäinen
Pekka
P
Salminen
Jukka
J
Salminen
Ulla-Stina
US
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*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab