Interferon-beta-1a induces increases in vascular cell adhesion molecule: implications for its mode of action in

J Graber1, M Zhan, D Ford

  • 1University of Maryland School of Medicine, Department of Neurology, Baltimore, MD, USA.

Insights

Interferon beta-1a treatment in Relapsing Remitting Multiple Sclerosis (RRMS) increases soluble VCAM (sVCAM) levels. Higher sVCAM levels correlate with fewer MRI lesions in patients receiving subcutaneous interferon beta-1a.

Area of Science:

  • Neuroimmunology
  • Biomarkers in Multiple Sclerosis

Background:

  • Relapsing Remitting Multiple Sclerosis (RRMS) is an autoimmune disease affecting the central nervous system.
  • Interferon beta (IFN-beta) is a common treatment for MS, but its precise mechanism of action is not fully understood.

Purpose of the Study:

  • To investigate the effect of two different administration schedules of IFN-beta-1a on soluble vascular cell adhesion molecule-1 (sVCAM) levels in RRMS patients.
  • To explore the correlation between sVCAM levels and MRI-detected lesions.

Main Methods:

  • Prospective study of 15 RRMS patients randomized to receive either once-weekly intramuscular (IM) IFN-beta-1a (30 mug) or three-times-weekly subcutaneous (SC) IFN-beta-1a (44 mug) for 24 weeks.
  • Measurement of sVCAM levels at baseline and during treatment.
  • Assessment of combined unique (CU) MRI lesions.

Main Results:

  • Both treatment groups showed a significant increase in sVCAM levels compared to pre-treatment.
  • The three-times-weekly SC IFN-beta-1a 44 mug group exhibited a significantly greater mean increase in sVCAM (321.9 ng/ml) compared to the once-weekly IM IFN-beta-1a 30 mug group (68.6 ng/ml).
  • A significant negative correlation was observed between CU MRI lesions and sVCAM levels in the SC IFN-beta-1a 44 mug group (p=0.009).

Conclusions:

  • IFN-beta therapy in MS may exert its effects, in part, by increasing sVCAM levels.
  • Elevated sVCAM may reduce T-cell adhesion to the blood-brain barrier (BBB) by binding to VLA-4, consistent with the observed reduction in MRI contrast-enhancing lesions.

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