Mechanisms of antifibrotic action of Interferon gamma-1b in pulmonary fibrosis

The pathology of progressive pulmonary fibrosis combines injury, chronic in flammation and exaggerated, but futile organ repair. Models of experimental organ fibrosis such as bleomycin- or irradiation-induced lung fibrosis ind icate that the continuous overexpression of major growth factors such as tr ansforming growth factor beta 1 plays a major role in the tissue reorganiza tion process and the modulation of the accompanying immune response. Moreov er, this process is combined with a reorganization of the extracellular mat rix 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 ch ronic cellular immune response shifts to the so-called T helper 2 type. Rec ent investigations have demonstrated that this poorly balanced immune respo nse 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 g amma-lb for the treatment of idiopathic pulmonary fibrosis, a relentlessly progressive form of human pulmonary fibrosis. This pilot investigation demo nstrated that interferon gamma is able to improve pulmonary function in pat ients with idiopathic pulmonary fibrosis while at the same time counterbala ncing mechanisms of exaggerated wound repair, such as the overinduction of transforming growth factor beta1.