Involvement of Cytokines in the Pathogenesis of Hypersensitivity Pneumonitis: Evaluation of Immunotherapeutic Measures in a Mouse Model
C57BL/6 inbred strain mice were instilled intranasally with 150 μg/day of the actinomycete Faeni rectivirgula three days a week as a model of farmer's lung disease. Instilled mice developed a strong alveolitis manifested by a large increase in the number of cells in the bronchoalveolar lavage (...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
1992-01-01
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| Series: | Canadian Journal of Infectious Diseases |
| Online Access: | http://dx.doi.org/10.1155/1992/875050 |
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| Summary: | C57BL/6 inbred strain mice were instilled intranasally with
150 μg/day of the actinomycete Faeni rectivirgula three days a week as a model of farmer's lung disease.
Instilled mice developed a strong alveolitis manifested by a large increase in the number of cells in the
bronchoalveolar lavage (BAL) (4.1 x 104 cells in saline controls versus 5.28x 105 cells in F rectivirgula-instilled
mice). This influx was associated with a substantial release of pro-inflanm1atory cytokine in the BAL; 170
U/mL of interleukin (IL)-1 in instilled mice whereas saline instilled mice had undetectable levels of cytokines
in the BAL. In addition, pulmonary fibrosis was evident in challenged mice at three weeks (twofold increase
in lung hydroxyproline levels). Infusion of a rabbit antimouse tumour necrosis factor-alpha was associated
with an almost complete abrogation of all markers of the disease. Also, administration of cyclosporine A
(50 mg/kg/day) partially prevented the alveolitis (P<0.01) and totally prevented cytokine release and lung
fibrosis in challenged mice. These findings underscore the tmmunological basis of hypersensitivity
pneumonitis, and suggest that antagonism of inflammatory cytokines may hold promise in the treatment
of this pathology. |
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| ISSN: | 1180-2332 |