VLA-4 expression on peripheral blood lymphocytes is downregulated after treatment of multiple sclerosis with interferon beta.
Adhesion molecules are likely to play a critical role in the immunopathogenesis of multiple sclerosis (MS). The interaction of vascular cell adhesion molecule-1 (VCAM-1) with its lymphocyte ligand very late antigen-4 (VLA-4) may mediate migration of lymphocytes into the CNS. We have previously demonstrated that MS patients treated with interferon beta (IFN-beta) have a significant increase in soluble VCAM-1 (sVCAM-1) soon after the initiation of treatment, and this effect correlated with the resolution of contrast-enhancing MRI lesions. We studied the cell surface expression of VLA-4 by flow cytometry in 10 MS patients before and during IFN-beta treatment. We found a significant decrease in mean VLA-4 fluorescence of MS patients' lymphocytes on treatment and no change in untreated controls. In vitro treatment of lymphocytes with IFN-beta did not reproduce this effect, but the addition of sVCAM-1 did result in a decrease in VLA-4 expression. These data indicate that the previously identified increase in sVCAM-1 may lead to a decrease in VLA-4 expression and that this effect may partially explain the mechanism of action of IFN-beta.
Calabresi
P A
PA
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1400, USA.
Pelfrey
C M
CM
Tranquill
L R
LR
Maloni
H
H
McFarland
H F
HF
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000906:Antibodies / Q000276:immunology; D017252:CD3 Complex / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000097:blood*; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000097:blood* / Q000276:immunology / Q000628:therapy*; D016201:Receptors, Lymphocyte Homing / Q000097:blood*
D000276:Adjuvants, Immunologic; D000906:Antibodies; D017252:CD3 Complex; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D016899:Interferon-beta