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

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-beta-1a 30 mu g intramuscularly (IM) (Group 1, 8 patients) or three-times-weekly (tiw) IFN-beta-1a 44 mu g 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-beta-1a 44 mu g 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-beta-1a 30 mu g IM qw (68.6 ng/ml). There was a negative correlation between combined unique (CU) MRI lesions and sVCAM levels within the IFN-beta-1a 44 mu g SC tiw group (slope=-0.00106, p=0.009). We postulate that the mode of action of IFN-beta 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-beta in reducing MRI contrast enhancing lesions. (C) 2004 Elsevier B.V. All rights reserved.