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This Article Full Text Full Text (PDF) All Versions of this Article: 285/6/L1255    most recent 00303.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Segel, M. J. Articles by Breuer, R. Search for Related Content PubMed PubMed Citation Articles by Segel, M. J. Articles by Breuer, R.

Role of interferon- in the evolution of murine bleomycin lung fibrosis

¹Lung Cellular & Molecular Biology Laboratory, Institute of Pulmonology, ²Bone Marrow Transplantation Department, Hadassah University Hospital and Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel; and ³Mallory Institute of Pathology, Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118

Submitted 14 September 2002 ; accepted in final form 27 June 2003

IFN- production is upregulated in lung cells (LC) of bleomycin-treated C57BL/6 mice. The present study characterizes the time course, cellular source, and regulation of IFN- expression in bleomycin-induced lung injury. IFN- mRNA in LC from bleomycin-treated mice peaked 3 days after intratracheal instillation. IFN- protein levels were increased at 6 days, as was the percentage of LC expressing IFN-. CD4⁺, CD8⁺, and natural killer cells each contributed significantly to IFN- production. IL-12 mRNA levels were increased at 1 day in LC of bleomycin-treated mice. Anti-IL-12 and anti-IL-18 antibodies decreased IFN- production by these cells. To define the role of endogenous IFN- in the evolution of bleomycin lung injury, we compared the effect of bleomycin in mice with a targeted knockout mutation of the IFN- gene (IFN- knockout) and wild-type mice. At 14 days after intratracheal bleomycin, total bronchoalveolar lavage cell counts and lung hydroxyproline were decreased in IFN- knockouts compared with wild-type animals. There was no difference in morphometric parameters of fibrosis. Our data show that enhanced IFN- production in the lungs of bleomycin-treated mice is at least partly IL-12 and IL-18 dependent. Absence of IFN- in IFN- knockout mice does not increase pulmonary fibrosis. Endogenous IFN- may play a proinflammatory or profibrotic role in bleomycin-induced lung fibrosis.

interstitial lung disease; transgenic/knockout; cytokines

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