INCREASES IN SOLUBLE VCAM-1 CORRELATE WITH A DECREASE IN MRI LESIONS IN MULTIPLE-SCLEROSIS TREATED WITH INTERFERON BETA-1B

Interferon beta-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 betwe en the levels of soluble adhesion molecules and a reduction in contras t-enhancing lesions on gadopentetate dimeglumine magnetic resonance im ages after treatment with interferon beta-1b. We determined levels of soluble vascular cell adhesion molecule-1, intercellular adhesion mole cule-1, E-selectin, L-selectin, and tumor necrosis factor receptor (60 kd) in monthly serum samples from patients with definite multiple scl erosis before and during treatment with interferon beta-1b. The level of soluble adhesion molecules was correlated with the number of newly enhancing lesions on monthly contrast-enhanced images. Levels of solub le vascular cell adhesion molecule during treatment were significantly increased compared to control or pretreatment values. The median leve ls (ng/ml) of this adhesion molecule were 580.3 (range; 373.0-640.7) f or 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 o ther soluble adhesion molecules and soluble tumor necrosis factor rece ptor 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 beta-1b by direct interference with the adhesion cascade, which may prevent a ctivated T cells from trafficking into the central nervous system.