Therapeutic targeting of alpha 4-integrins in chronic inflammatory diseases: tipping the scales of risk towards benefit?

Eur J Immunol. 2005 Aug;35(8):2268-73. doi: 10.1002/eji.200535195.


Inhibition of leukocyte trafficking via alpha4-integrin antibody blockade has recently become a validated therapeutic approach for several inflammatory diseases, including multiple sclerosis, ulcerative colitis and Crohn's disease. In the midst of this recent success, 3 patients receiving chronic treatment with the anti-alpha4 antagonist natalizumab (Tysabri) for the treatment of multiple sclerosis or Crohn's disease, developed JC-virus related progressive multifocal leukoencephalopathy (PML). These unforeseen consequences suggest that long term blockade of alpha4-integrins might prevent trafficking of non-pathogenic lymphocytes that are essential for viral immunosurveillance. In the current issue of the European Journal of Immunology Bjursten and colleagues report that long term treatment with anti-alpha4-integrin antibodies results in exacerbation of the murine model of colitis induced by the targeted deletion of the heterotrimeric G protein subunit Galphai2. In order to properly evaluate the efficacy and safety of anti-alpha4-integrin therapy, the relationship between these observations in an immunologically altered animal model and human clinical disease needs to be carefully measured.

Publication types

  • Review

MeSH terms

  • Animals
  • Chronic Disease
  • Disease Models, Animal
  • Humans
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / therapy*
  • Integrin alpha4 / metabolism*


  • Integrin alpha4