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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1991-12-17
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pubmed:abstractText |
We examined the importance of the cytokine tumor necrosis factor-alpha (TNF-alpha) 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 micrograms 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-alpha (up to 80 U/ml of TNF-alpha in the bronchoalveolar lavage [BAL] at 3 wk after beginning of treatment) and interleukin-1, which peaked at 1 wk (approximately 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-alpha 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-alpha (2 mg/wk) completely abrogated the disease, as mice so treated had normal lung histology. Anti-TNF-alpha blocked cellular recruitment in the lungs (only a 2-fold increase at week 3); it also completely abolished TNF-alpha secretion in the BAL and drastically reduced interleukin-1 levels in this fluid. Anti-TNF-alpha also abolished lung index increases and lung fibrosis, with both parameters similar to that of saline-instilled mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1044-1549
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
477-83
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:1931076-Alveolitis, Extrinsic Allergic,
pubmed-meshheading:1931076-Animals,
pubmed-meshheading:1931076-Disease Models, Animal,
pubmed-meshheading:1931076-Immune Sera,
pubmed-meshheading:1931076-Kinetics,
pubmed-meshheading:1931076-Lung,
pubmed-meshheading:1931076-Mice,
pubmed-meshheading:1931076-Mice, Inbred C57BL,
pubmed-meshheading:1931076-Saccharopolyspora,
pubmed-meshheading:1931076-Tumor Necrosis Factor-alpha
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pubmed:year |
1991
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pubmed:articleTitle |
Tumor necrosis factor plays an essential role in determining hypersensitivity pneumonitis in a mouse model.
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pubmed:affiliation |
Unité de recherche, Centre de Pneumologie, Hôpital Laval, Sainte-Foy, Quebec, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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