Elevation of serum thioredoxin in patients with gefitinib-induced interstitial lung disease.

OBJECTIVE Interstitial lung disease (ILD) is a severe adverse event of gefitinib therapy. However, the mechanism still remains unclear. The objective of this study was to examine whether or not oxidative stress, one of the common factors in drug-associated ILD, is involved in the pathogenesis of gefitinib-induced ILD. PATIENTS AND METHODS Using an enzyme-linked immunosorbent assay (ELISA), we measured the concentration of serum thioredoxin (Trx), a redox-active protein with antioxidative effects, in 44 patients treated with gefitinib, including three patients who had ILD. RESULTS In patients who had gefitinib-induced ILD, serum Trx levels were significantly elevated. They decreased after cessation of gefitinib therapy accompanying clinical improvement of ILD. CONCLUSION It was suggested that oxidative stress may be involved as a part of mechanisms causing or worsening gefitinib-induced ILD.

[1]  A. Nicholson,et al.  Extracellular thioredoxin levels are increased in patients with acute lung injury , 2006, Thorax.

[2]  M. Tanito,et al.  Thioredoxin-1 suppresses lung injury and apoptosis induced by diesel exhaust particles (DEP) by scavenging reactive oxygen species and by inhibiting DEP-induced downregulation of Akt. , 2005, Free radical biology & medicine.

[3]  S. Kudoh,et al.  Interstitial lung disease associated with drug therapy , 2004, British Journal of Cancer.

[4]  K. Nozaki,et al.  Intravenous administration of thioredoxin decreases brain damage following transient focal cerebral ischemia in mice. , 2004, Antioxidants & redox signaling.

[5]  近藤 則彦 Redox-sensing release of human thioredoxin from T lymphocytes with negative feedback loops , 2004 .

[6]  J. Yodoi,et al.  Redox-active protein thioredoxin prevents proinflammatory cytokine- or bleomycin-induced lung injury. , 2003, American journal of respiratory and critical care medicine.

[7]  J. Yodoi,et al.  Elevated serum levels of thioredoxin in patients with acute exacerbation of asthma. , 2003, Immunology letters.

[8]  J. Yodoi,et al.  Enhanced resistancy of thioredoxin-transgenic mice against influenza virus-induced pneumonia. , 2002, Immunology letters.

[9]  J. Yodoi,et al.  Thioredoxin as a biomarker for oxidative stress in patients with rheumatoid arthritis. , 2002, Molecular immunology.

[10]  角田 圭雄 Serum thioredoxin levels as an indicator of oxidative stress in patients with hepatitis C virus infection , 2002 .

[11]  L. Herzenberg,et al.  Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[12]  C. Arteaga,et al.  Tyrosine kinase inhibitors—ZD1839 (Iressa) , 2001, Current opinion in oncology.

[13]  H. Nakamura,et al.  Serum thioredoxin (TRX) levels in patients with heart failure. , 2001, Japanese circulation journal.

[14]  T. Horie,et al.  Expression of thioredoxin in bleomycin-injured airway epithelium: possible role of protection against bleomycin induced epithelial injury. , 2001, Life Science.

[15]  P. Ghezzi,et al.  Chronic elevation of plasma thioredoxin: Inhibition of chemotaxis and curtailment of life expectancy in AIDS , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  B. Sahaf,et al.  Thioredoxin blood level increases after severe burn injury. , 2000, Antioxidants & redox signaling.

[17]  D. Mustacich,et al.  The role of the redox protein thioredoxin in cell growth and cancer. , 2000, Free radical biology & medicine.

[18]  Y. Yamaoka,et al.  Expression of thioredoxin and glutaredoxin, redox-regulating proteins, in pancreatic cancer. , 2000, Cancer detection and prevention.

[19]  T. Sugimura,et al.  EIevated serum level of Thioredoxin in patients with Hepatocellular Carcinoma , 1998 .

[20]  M. Roederer,et al.  Elevation of plasma thioredoxin levels in HIV-infected individuals. , 1996, International immunology.

[21]  Y. Fujiwara,et al.  Sensitive enzyme‐linked immunosorbent assay for adult T‐cell leukemia‐derived factor and normal value measurement , 1996, Journal of clinical laboratory analysis.