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Tumor necrosis factor/cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis

Published in The Journal of experimental medicine. 1989, vol. 170, no. 3, p. 655-63
Abstract The role of TNF-alpha/cachectin in the pneumopathy elicited by bleomycin has been investigated. After a single intratracheal bleomycin instillation, an increase of the lung TNF-alpha mRNA level was evident, from days 5 to 15, as shown by Northern gel analysis of whole lung RNA. In contrast, lung IL-1-alpha and GM-CSF mRNA were not detectable. In mice passively immunized with rabbit anti-mouse TNF-alpha IgG, the bleomycin-induced collagen deposition, evaluated by the total lung hydroxyproline assay on day 15, was prevented. Depletion of the CD4 and CD8 T lymphocytes by an in vivo treatment with mAb prevented the bleomycin-induced increase of TNF mRNA level and fibrosis. After an administration of bleomycin in continuous intraperitoneal perfusion, the diffuse alveolar damage observed by light and electron microscopy was almost completely prevented by anti-TNF antibody. These results indicate that in response to bleomycin, the T lymphocytes induce, by an undefined mechanism, an increase of the pulmonary TNF production, which leads to alveolar damage, growth of fibroblast, and collagen deposition.
Keywords AnimalsBleomycin/toxicityCollagen/metabolismImmunoglobulin G/immunologyLung/drug effects/pathologyMiceMice, Inbred C57BLMice, Inbred CBAPulmonary Fibrosis/chemically inducedRNA, Messenger/analysisRabbitsT-Lymphocytes/physiologyTumor Necrosis Factor-alpha/genetics/immunology/physiology
PMID: 2475571
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Research group Caractérisation génétique et biochimique du complexe Ccr4-Not conservé (81)
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PIGUET, Pierre et al. Tumor necrosis factor/cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis. In: The Journal of experimental medicine, 1989, vol. 170, n° 3, p. 655-63. doi: 10.1084/jem.170.3.655 https://archive-ouverte.unige.ch/unige:30050

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Deposited on : 2013-10-01

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