The effect of interferon β-1b on lymphocyte-endothelial cell adhesion

Suhayl Dhib-Jalbut, Hong Jiang, Gary J. Williams

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42 Scopus citations

Abstract

Interferon β-1b (IFNβ-1b) (Betaseron®) has been recently approved for treatment of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). The mechanism of action of IFNβ-1b is not understood, but its effect in reducing gadolinium enhanced MRI lesions suggest an effect at the blood brain barrier (BBB). Thus the objective of this study is to examine the effect of IFNβ-1b treatment of endothelial cells (EC) on lymphocyte-EC adhesion, and on the expression of the adhesion molecules (AM) ICAM-1, VCAM and E-selectin induced by IFN-γ, TNF-α, or IL-1β. Primary cultures of human umbilical vein EC (HUVEC) were used which under basal conditions expressed low levels of ICAM-1 but not VCAM or E-selectin. IFNβ-1b (1-1000 IU/ml) had minimal effect on basal expression of AM on HUVEC, but AM could be substantially upregulated by IFN-γ, IL-1β or TNF-α which was associated with a parallel increase in lympbocyte-EC adhesion. The effect of IFNβ-1b on AM expression induced by IFN-γ, IL-1β or TNF-α was slightly additive, and was associated with a modest increase in lymphocyte-EC adhesion. In contrast TGF-β, shown previously to dowregulate lymphocyte-EC adhesion, inhibited this adhesion in our experiments. It is concluded that IFN-β does not downregulate the inducible expression of ICAM-1, VCAM or E-selectin on HUVEC and does not inhibit the adhesion of lymphocytes to HUVEC. These findings have implications on the mechanism of action of IFNβ-1b in MS.

Original languageEnglish (US)
Pages (from-to)215-222
Number of pages8
JournalJournal of Neuroimmunology
Volume71
Issue number1-2
DOIs
StatePublished - Dec 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Keywords

  • adhesion molecules
  • endothelial cells
  • interferon β-1b
  • multiple sclerosis

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