Interstitial pulmonary fibrosis (IPF) is a devastating disease for which current therapy is minimally effective. Colchicine, an inhibitor of collagen synthesis and secretion, promotes collagenolytic activity, and suppresses the release of some fibroplast growth factors by alveolar macrophages. Interferon gamma 1-b (IFN-γ), an attractive therapeutic candidate, it regulates both macrophages and fibroplast functions. Transforming growth factor β1 (TGF-β1) antagonizes all antifibrotic actions of IFN-γ and connective-tissue growth factor (CTGF) is the major mediator of TGF-β1. The level of transcription of IFN-γ, TGF-β1 and CTGF genes before and after treatment with IFN-gamma-1b or Colchicine in patients with IPF was evaluated.
Two groups of patients were studied. The first 6 patients was treated with IFN-gamma-1b, while the second with Colchicine, 4 patients. Open lung and transbronchial biopsy specimens were obtained before treatment and after 6 and 18 months of therapy. Total RNA was extracted from all patients at all three time points (0,6,18 months) using reverse-transcription polymerase chain reaction (RT-PCR) assay we compared the transcription levels of TGF-β1, CTGF, and IFN-γ genes in both groups of patients.
Before treatment, all patients exhibited marked mRNA_expression of TGF-β1 and CTGF, but no transcription of IFN-γ. After treatment all patients presented decreased TGFβ1 mRNA expression. In the IFN-γ group three patients (50%) showed transcription of IFN-γ gene at 6 (1 patient) and at 18 months (2 patients) after treatment. Two patients (50%)in the Colchicine group presented expression of IFN-γ mRNA. The expression of CTGF gene remained almost stable (non noticeable differences) before and after treatment in both groups. ELISA analysis of bronchoalveolar lavage fluid (BALF) for these molecules is underway.
Both treatments give evidence of inhibiting mRNA expression of TGF-β1 and enhancing of IFN-γ transcription.
IFN-gamma (IFN-γ), whose production is impaired in IPF, could be a promising novel treatment in patients with IPF.
K.M. Antoniou, None.