Mechanisms of antifibrotic action of interferon gamma-1b in pulmonary fibrosis.
The pathology of progressive pulmonary fibrosis combines injury, chronic inflammation and exaggerated, but futile organ repair. Models of experimental organ fibrosis such as bleomycin- or irradiation-induced lung fibrosis indicate that the continuous overexpression of major growth factors such as transforming growth factor beta 1 plays a major role in the tissue reorganization process and the modulation of the accompanying immune response. Moreover, this process is combined with a reorganization of the extracellular matrix that is likely to allow for the secondary loss of transcription of the interferon gamma gene. As a result, the cytokine pattern of the evolving chronic cellular immune response shifts to the so-called T helper 2 type. Recent investigations have demonstrated that this poorly balanced immune response is a characteristic feature of human progressive lung fibrosis such as idiopathic pulmonary fibrosis. Based on the strong antifibrotic properties of interferon gamma, we combined low-dose glucocorticoids with interferon gamma-1b for the treatment of idiopathic pulmonary fibrosis, a relentlessly progressive form of human pulmonary fibrosis. This pilot investigation demonstrated that interferon gamma is able to improve pulmonary function in patients with idiopathic pulmonary fibrosis while at the same time counterbalancing mechanisms of exaggerated wound repair, such as the overinduction of transforming growth factor beta 1.
Ziesche
R
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Department of Internal Medicine IV, University of Vienna, Austria.
Block
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D000818:Animals; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000009:adverse effects; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology; D053773:Transforming Growth Factor beta1; D016896:Treatment Outcome
D005938:Glucocorticoids; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma