Title: Tumor Necrosis Factor Plays an Essential Role in Determining Hypersensitivity Pneumonitis in a Mouse Model
Abstract: We examined the importance of the cytokine tumor necrosis factor-α (TNF-α) in a mouse model of hypersensitivity pneumonitis (HP). Mice of the C57BL/6 strain were instilled intranasally 3 days/wk for 3 wk with 150 µg of the actinomycete Faenia rectivirgula (Micropolyspora faeni) to induce HP as a model of farmer's lung. This experimental model was associated with a progressive inflammation in the lungs of challenged mice, seen histologically as cellular infiltrates of large quantities of macrophages and lymphocytes and some neutrophils. The disease in challenged mice treated with a control rabbit serum was also associated with a substantial release of tumor TNF-α (up to 80 U/ml of TNF-α in the bronchoalveolar lavage [BAL] at 3 wk after beginning of treatment) and interleukin-1, which peaked at 1 wk (∼300 U/ml) and diminished thereafter. A very large increase in BAL cell number (11-fold increase versus saline controls) and an enhanced release potential for TNF-α by alveolar macrophages was also seen. Lung fibrosis was also evident in challenged animals, as demonstrated by a 2-fold increase in hydroxyproline levels. Infusion of challenged mice with a rabbit polyclonal antibody against TNF-α (2 mg/wk) completely abrogated the disease, as mice so treated had normal lung histology. Anti-TNF-α blocked cellular recruitment in the lungs (only a 2-fold increase at week 3); it also completely abolished TNF-α secretion in the BAL and drastically reduced interleukin-1 levels in this fluid. Anti-TNF-α also abolished lung index increases and lung fibrosis, with both parameters similar to that of saline-instilled mice. These findings indicate a crucial role for TNF-α in the development of experimental HP.
Publication Year: 1991
Publication Date: 1991-11-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 85
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