Clinical, radiological and molecular effects in three patients with idiopathic pulmonary fibrosis after long-term treatment with interferon gamma-1b

BACKGROUND: Interferon gamma-1b (IFN-y-lb), an antifibrotic agent, has been proposed as a novel therapeutic agent or idiopathic pulmonary fibrosis (IPF). The long-term clinical and olecular effects of this agent are still unknown. Experience with three IPF patients treated with IFN-y-1b for 4-7 consecutive years is reported. OBJECTIVES:Three patients with histologically proven IPF were studied prospectively. They received IFN-y-1b 200 mu g subcutaneously, three times weekly, along with low-dose prednisolone. The patients were monitored for at least four years according the ATS/ERS criteria and the appearance of the lesions on high resolution computed tomography (HRCT). METHODS: Using RT-PCR assay, the transcription levels of transforming growth factor beta 1(TGF-beta 1), connective tissue growth factor (CTGF), and interferon-gamma (IFN gamma) genes in lung tissue were evaluated before, and after two years of treatment. RESULTS: Treatment was well tolerated and no acute exacerbation of the disease was observed in any patient. Pulmonary fibrosis remained stable in terms of symptoms and pulmonary function tests (PFTs), and improvement in HRCT scoring was detected in o of the three patients. Marked mRNA expression of TGF-beta 1 and CTGF, but complete lack of IFN-gamma was detected in fibrotic lung tissue at baseline. After two years of treatment, all three patients exhibited increased expression of the IFN-gamma gene (p<0.05), while TGF-beta 1 and CTGF transcriptional levels had not changed. CONCLUSIONS: Longterm treatment with IFN-y-lb in patients with mild-to-moderate IPF appears to be safe. In two of the three patients monitored, the disease was stabilized, probably by enhancement of the expression of the IFN-gamma endogenous gene.