The effect of interferon beta-1b on cytokine-induced adhesion molecule expression

Interferon beta-1b (IFN beta-1b) (Betaseron) has been recently shown to alter the course of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) where migration of activated lymphocytes across the blood-brain barrier (BBB) is a critical step in the pathogenesis of this disease. Magnetic resonance imaging (MRI) studies performed on patients treated with IFN beta-1b showed a remarkable effect on the BBB as determined by a reduction in the number of gadolinium enhancing lesions, a measure of BBB leakiness. Since adhesion molecules (AM) induced on endothelial cells (EC) play an important role in T-cell migration into the CNS, the objective of this study was to examine the effect of IFN beta-1b on the expression of the AM, ICAM-1, V-CAM and E-selection induced on EC by IFN-gamma, TNF-alpha, or IL-1 beta. Primary cultures of human umbilical vein EC (HUVEC) were used, which under basal conditions expressed low levels of AM. IFN beta-1b (1-1000IU/ml) had minimal effect on basal expression of AM on HUVEC, but AM could be substantially upregulated by IFN-gamma, IL-1 beta or TNF-alpha. The effect of IFN beta-1b on AM expression induced by IFN-gamma, IL-1 beta or TNF-alpha was slightly additive. It is concluded that IFN beta-1b does not downregulate the inducible expression of ICAM-1, V-CAM or E-selectin on HUVEC. These findings suggest alternate mechanisms for the effect of IFN beta-1b on the BBB in MS.