The effect of interferon beta-1b on lymphocyte-endothelial cell adhesion.
Interferon beta-1b (IFN beta-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 IFN beta-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 IFN beta-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-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 ICAM-1 but not VCAM or E-selectin. IFN beta-1b (1-1000 IU/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 which was associated with a parallel increase in lymphocyte-EC adhesion. The effect of IFN beta-1b on AM expression induced by IFN-gamma, IL-1 beta or TNF-alpha was slightly additive, and was associated with a modest increase in lymphocyte-EC adhesion. In contrast TGF-beta, shown previously to downregulate lymphocyte-EC adhesion, inhibited this adhesion in our experiments. It is concluded that IFN-beta 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 IFN beta-1b in MS.
Dhib-Jalbut
S
S
Department of Neurology, University of Maryland Hospital, Baltimore 21201, USA.
Jiang
H
H
Williams
G J
GJ
D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology*; 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 / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology*; D009103:Multiple Sclerosis / Q000503:physiopathology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D019040:E-Selectin; 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