title: Effects of antifibrotic agents on TGF-beta1, CTGF and IFN-gamma expression in patients with idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is a deadly disease, largely unresponsive to treatment with corticosteroids and immunosuppressives. The aim of this randomized, prospective, open-label study was to characterize the molecular effects of IFN-gamma-1b and colchicine, on biomarkers expression associated with fibrosis (TGF-beta, CTGF) and immunomodulatory/antimicrobial activity (IFN-gamma), in the lungs of patients with IPF. Fourteen (14) patients with an established diagnosis of IPF received either 200 microg of IFN-gamma-1b subcutaneously three times per week, or 1mg of oral colchicine per day, for 24 months. Using RT-PCR assay, we evaluated the transcription levels of transforming growth factor beta1 (TGF-beta1), connective-tissue growth factor (CTGF), and interferon-gamma (IFN-gamma) genes in lung tissue before and after treatment with IFN-gamma-1b or colchicine. Marked mRNA expression of TGF-beta1 and CTGF, but complete lack of interferon-gamma was detected in fibrotic lung tissue at entry. After treatment, both groups exhibited increased expression of IFN-gamma gene at 6 months that was sustained at 24 months. The expression of CTGF and TGF-beta1 remained almost stable before and after treatment, in the IFN-gamma-1b group, while TGF-beta1 was statistically decreased after therapy, in the colchicine group (p=0.0002). Significant difference in DLCO (% pred), was found between the two treatment groups in favor of IFN-gamma-1b group (p=0.04). In addition, the IFN-gamma-1b group showed stability in arterial PO2 while the colchicine group significantly deteriorated (p=0.02). In conclusion, we report the effect of antifibrotic agents (IFN-gamma-1b and colchicine) in TGF-beta, CTGF, and endogenous IFN-gamma gene expression, in human fibrosis. However, extended studies are needed to verify the pathophysiological consequences of these findings.
authors: Department of Thoracic Medicine, Medical School University of Crete, 71110 Heraklion, Crete, Greece.
authors: Eleni G
authors: EG
authors: Tzortzaki
authors: Katerina M
authors: KM
authors: Antoniou
authors: Maria I
authors: MI
authors: Zervou
authors: Irini
authors: I
authors: Lambiri
authors: Anastassios
authors: A
authors: Koutsopoulos
authors: Nikolaos
authors: N
authors: Tzanakis
authors: Maria
authors: M
authors: Plataki
authors: George
authors: G
authors: Maltezakis
authors: Demosthenes
authors: D
authors: Bouros
authors: Nikolaos M
authors: NM
authors: Siafakas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003078:Colchicine / Q000627:therapeutic use*; D055513:Connective Tissue Growth Factor; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use*; D011446:Prospective Studies; D011658:Pulmonary Fibrosis / Q000188:drug therapy*; D011994:Recombinant Proteins; D012129:Respiratory Function Tests; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D050257:Tubulin Modulators / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D050257:Tubulin Modulators; D055513:Connective Tissue Growth Factor; D007371:Interferon-gamma; D011239:Prednisolone; D003078:Colchicine