VLA-4 EXPRESSION ON PERIPHERAL-BLOOD LYMPHOCYTES IS DOWN-REGULATED AFTER TREATMENT OF MULTIPLE-SCLEROSIS WITH INTERFERON-BETA

Adhesion molecules are likely to play a critical role in the immunopat hogenesis of multiple sclerosis (MS). The interaction of vascular cell adhesion molecule-1 (VCAM-1) with its lymphocyte Ligand very late ant igen-4 (VLA-4) may mediate migration of lymphocytes into the CNS. We h ave previously demonstrated that MS patients treated with interferon b eta (IFN-beta) have a significant increase in soluble VCAM-1 (sVCAM-1) soon after the initiation of treatment, and this effect correlated wi th the resolution of contrast-enhancing MRI lesions. We studied the ce ll surface expression of VLA-4 by flow cytometry in 10 MS patients bef ore and during IFN-beta treatment. We found a significant decrease in mean VLA-4 fluorescence of MS patients' lymphocytes on treatment and n o change in untreated controls. In vitro treatment of lymphocytes with IFN-beta did not reproduce this effect, but the addition of sVCAM-1 d id result in a decrease in VLA-4 expression. These data indicate that the previously identified increase in sVCAM-1 may lead to a decrease i n VLA-4 expression and that this effect may partially explain the mech anism of action of IFN-beta.