Thalidomide has a therapeutic effect on interstitial lung fibrosis: evidence from in vitro and in vivo studies

Clin Exp Immunol. 2009 Aug;157(2):310-5. doi: 10.1111/j.1365-2249.2009.03962.x.


The objective of this study was to investigate the effects of thalidomide (THD) on interstitial lung fibrosis (ILF). In vitro, human fetal lung fibroblast (HFL-F) to myofibroblast (MF) trans-differentiation was induced by transforming growth factor (TGF)-beta1. The effects of THD on trans-differentiation process or differentiated MF were evaluated by measuring hydroxyproline (HYP) content by alkaline hydrolysis colorimetry, alpha-smooth muscle actin (alpha-SMA) protein by Western blot and alpha-SMA and pro-collagen III mRNA expressions by semi-quantitative reverse transcription-polymerase chain reaction; in vivo, a mouse model of ILF was generated by daily subcutaneous injection of bleomycin (BLM) in female C3H mice. Gastric perfusion of THD began 1 week prior to injection and lasted for 8 weeks. Lung specimens were harvested at different time-points (1, 4, 6 and 8 weeks) for pathology and immunohistochemistry examination. The HYP content, alpha-SMA and pro-collagen III mRNA expressions were also assessed. THD inhibited the up-regulation of HYP protein, pro-collagen III mRNA and alpha-SMA protein induced by TGF-beta1 in HFL-F cells, and additionally inhibited pro-collagen III mRNA expression on trans-differentiated MF. THD reduced HYP synthesis in the lung tissues of BLM-treated mice at week 4, and slightly reduced the numbers of alpha-SMA-positive cells. THD had an effect on ILF models both in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Animals
  • Bleomycin
  • Blotting, Western / methods
  • Cell Differentiation
  • Cells, Cultured
  • Collagen Type III / genetics
  • Female
  • Fibroblasts / pathology
  • Humans
  • Hydroxyproline / genetics
  • Immunohistochemistry
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / immunology
  • Lung Diseases, Interstitial / pathology
  • Mice
  • Mice, Inbred Strains
  • Models, Animal
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Scleroderma, Systemic / drug therapy
  • Scleroderma, Systemic / immunology
  • Scleroderma, Systemic / pathology
  • Thalidomide / pharmacology
  • Thalidomide / therapeutic use*
  • Transforming Growth Factor beta1 / antagonists & inhibitors*
  • Transforming Growth Factor beta1 / immunology
  • Transforming Growth Factor beta1 / pharmacology


  • Actins
  • Collagen Type III
  • Immunosuppressive Agents
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Bleomycin
  • Thalidomide
  • Hydroxyproline