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.
Jiang
H
H
Department of Neurology, University of Maryland, Baltimore, USA.
Williams
G J
GJ
Dhib-Jalbut
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000276:Adjuvants, Immunologic; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007371:Interferon-gamma; D000068556:Interferon beta-1a