Increases in soluble VCAM-1 correlate with a decrease in MRI lesions in multiple sclerosis treated with interferon β-1b

Authors

  • Dr Peter A. Calabresi MD,

    Corresponding author
    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Scottsdale, AZ
    • Neuroimmunology Branch, NINDS, National Institutes of Health, Building 10, Room 5b-16, 10 Center Drive, MSC-1400, Bethesda, MD 20892-1400
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  • Laura R. Tranquill MS,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Scottsdale, AZ
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  • James M. Dambrosia PhD,

    1. Biometry and Field Studies Branch, National Institute of Neurological Disorders and Stroke, Scottsdale, AZ
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  • Lael A. Stone MD,

    1. Department of Neurology, Mayo Clinic Scottsdale, Scottsdale, AZ
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  • Heidi Maloni RN,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Scottsdale, AZ
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  • Craig N. Bash MD,

    1. Laboratory for Diagnostic Radiology Research of the Office of the Director of the National Institutes of Health, National Institutes of Health, Bethesda, MD, Scottsdale, AZ
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  • Joseph A. Frank MD,

    1. Laboratory for Diagnostic Radiology Research of the Office of the Director of the National Institutes of Health, National Institutes of Health, Bethesda, MD, Scottsdale, AZ
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  • Henry F. McFarland MD

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Scottsdale, AZ
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Abstract

Interferon β-1b reduces clinical exacerbations and disease activity in multiple sclerosis as shown by magnetic resonance imaging, but the mechanism of action is unknown. We investigated the correlation between the levels of soluble adhesion molecules and a reduction in contrast-enhancing lesions on gadopentetate dimeglumine magnetic resonance images after treatment with interferon β-1b. We determined levels of soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, L-selectin, and tumor necrosis factor receptor (60 kd) in monthly serum samples from patients with definite multiple sclerosis before and during treatment with interferon β-1b. The level of soluble adhesion molecules was correlated with the number of newly enhancing lesions on monthly contrast-enhanced images. Levels of soluble vascular cell adhesion molecule during treatment were significantly increased compared to control or pretreatment values. The median levels (ng/ml) of this adhesion molecule were 580.3 (range; 373.0–640.7) for the healthy subjects, and 551.4 (489.7–875.5) for patients prior to treatment and 847.9 (591.5–1,232.9) during treatment. Levels of the other soluble adhesion molecules and soluble tumor necrosis factor receptor were not significantly changed during treatment. The increase in soluble vascular cell adhesion molecule correlated with a decrease in the number of contrast-enhancing lesions on magnetic resonance images. These data suggest a novel mechanism of action for interferon β-1b by direct interference with the adhesion cascade, which may prevent activated T cells from trafficking into the central nervous system.

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