Effects of antifibrotic agents on TGF-beta1, CTGF and IFN-gamma expression in patients with idiopathic pulmonary fibrosis

Respir Med. 2007 Aug;101(8):1821-9. doi: 10.1016/j.rmed.2007.02.006. Epub 2007 Mar 27.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Colchicine / therapeutic use*
  • Connective Tissue Growth Factor
  • Female
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interferon-gamma / therapeutic use*
  • Male
  • Middle Aged
  • Prednisolone / therapeutic use*
  • Prospective Studies
  • Pulmonary Fibrosis / drug therapy*
  • Recombinant Proteins
  • Respiratory Function Tests
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Tubulin Modulators / therapeutic use*


  • Antineoplastic Agents
  • CCN2 protein, human
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Tubulin Modulators
  • Connective Tissue Growth Factor
  • Interferon-gamma
  • Prednisolone
  • Colchicine