Interferon-β-1a induces increases in vascular cell adhesion molecule: Implications for its mode of action in multiple sclerosis

J. Graber, M. Zhan, D. Ford, F. Kursch, G. Francis, C. Bever, H. Panitch, P. A. Calabresi, S. Dhib-Jalbut

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

We investigated soluble vascular cell adhesion molecule-1 (sVCAM) levels and MRI lesions over 24 weeks in 15 Relapsing Remitting MS (RRMS) patients randomized prospectively to receive once-weekly (qw) IFN-β-1a 30 μg intramuscularly (IM) (Group I, 8 patients) or three-times-weekly (tiw) IFN-β-1a 44 μg subcutaneously (SC) (Group II, 7 patients). Both groups demonstrated a significant increase in sVCAM during treatment when compared to pre-treatment levels. Patients on IFN-β-1a 44 μg SC tiw had a significant (p<0.0001) mean increase in sVCAM of 321.9 ng/ml which was significantly greater (p<0.0001) than with IFN-β-1a 30 μg IM qw (68.6 ng/ml). There was a negative correlation between combined unique (CU) MRI lesions and sVCAM levels within the IFN-β-1a 44 μg SC tiw group (slope=-0.00106, p=0.009). We postulate that the mode of action of IFN-β therapy in MS may involve the induction of an increase in sVCAM. sVCAM could bind VLA-4 on T-cells and intercept their adhesion to the blood brain barrier (BBB). This mechanism is consistent with the observed clinical effect of IFN-β in reducing MRI contrast enhancing lesions.

Original languageEnglish (US)
Pages (from-to)169-176
Number of pages8
JournalJournal of Neuroimmunology
Volume161
Issue number1-2
DOIs
StatePublished - Apr 2005

Keywords

  • Interferon-beta (IFN-β-1a)
  • Multiple sclerosis
  • Vascular cell adhesion molecule (VCAM)
  • Very late antigen-4 (VLA-4)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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    Graber, J., Zhan, M., Ford, D., Kursch, F., Francis, G., Bever, C., Panitch, H., Calabresi, P. A., & Dhib-Jalbut, S. (2005). Interferon-β-1a induces increases in vascular cell adhesion molecule: Implications for its mode of action in multiple sclerosis. Journal of Neuroimmunology, 161(1-2), 169-176. https://doi.org/10.1016/j.jneuroim.2004.11.017