Elsevier

Cytokine

Volume 15, Issue 3, August 2001, Pages 138-147
Cytokine

Regular Articles
LUNG INTERLEUKIN-4 GENE EXPRESSION IN A MURINE MODEL OF BLEOMYCIN-INDUCED PULMONARY FIBROSIS

https://doi.org/10.1006/cyto.2001.0903Get rights and content

Abstract

Interleukin-4 (IL-4) is known to activate mononuclear cells as well as fibroblasts, all of which are important in the pathogenesis of pulmonary fibrosis. To investigate the potential role of this cytokine, lung IL-4 expression was examined in a murine model of bleomycin-induced pulmonary fibrosis. Lung fibrosis was induced in CBA/J mice by endotracheal injection of bleomycin on day 0. On selected days after treatment, lungs were harvested for reverse transcriptase polymerase chain reaction (RT-PCR), Northern, in-situ hybridization and immunohistochemical analyses. RT-PCR and Northern analyses revealed significant increases in lung IL-4 mRNA content between days 3 and 14 after induction of lung injury, which decreased toward control level after day 21. Both in-situ hybridization and immunohistochemistry showed low or undetectable IL-4 expression in control lungs and in injured lungs before day 3 after bleomycin injection. There was however elevated expression in mononuclear cells and macrophages between days 3 and 14, localized to areas of active fibrosis. These results demonstrate that IL-4 is upregulated significantly in this model. They suggest a potential role for this cytokine in pulmonary fibrosis, perhaps via its ability to stimulate and amplify the inflammatory response, stimulate collagen synthesis in fibroblasts, and thus promote the progression to fibrosis and end stage lung disease.

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    f2

    Current address: Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan

    f1

    Correspondence to: Sem H. Phan, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA. E-mail:[email protected]

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