Interferon-β-1a induces increases in vascular cell adhesion molecule

Implications for its mode of action in multiple sclerosis

J. Graber, M. Zhan, D. Ford, F. Kursch, G. Francis, C. Bever, H. Panitch, P. A. Calabresi, S. Dhib-Jalbut

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

We investigated soluble vascular cell adhesion molecule-1 (sVCAM) levels and MRI lesions over 24 weeks in 15 Relapsing Remitting MS (RRMS) patients randomized prospectively to receive once-weekly (qw) IFN-β-1a 30 μg intramuscularly (IM) (Group I, 8 patients) or three-times-weekly (tiw) IFN-β-1a 44 μg subcutaneously (SC) (Group II, 7 patients). Both groups demonstrated a significant increase in sVCAM during treatment when compared to pre-treatment levels. Patients on IFN-β-1a 44 μg SC tiw had a significant (p<0.0001) mean increase in sVCAM of 321.9 ng/ml which was significantly greater (p<0.0001) than with IFN-β-1a 30 μg IM qw (68.6 ng/ml). There was a negative correlation between combined unique (CU) MRI lesions and sVCAM levels within the IFN-β-1a 44 μg SC tiw group (slope=-0.00106, p=0.009). We postulate that the mode of action of IFN-β therapy in MS may involve the induction of an increase in sVCAM. sVCAM could bind VLA-4 on T-cells and intercept their adhesion to the blood brain barrier (BBB). This mechanism is consistent with the observed clinical effect of IFN-β in reducing MRI contrast enhancing lesions.

Original languageEnglish (US)
Pages (from-to)169-176
Number of pages8
JournalJournal of Neuroimmunology
Volume161
Issue number1-2
DOIs
StatePublished - Apr 2005
Externally publishedYes

Fingerprint

Vascular Cell Adhesion Molecule-1
Interferons
Multiple Sclerosis
Integrin alpha4beta1
Blood-Brain Barrier
Therapeutics
T-Lymphocytes

Keywords

  • Interferon-beta (IFN-β-1a)
  • Multiple sclerosis
  • Vascular cell adhesion molecule (VCAM)
  • Very late antigen-4 (VLA-4)

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Interferon-β-1a induces increases in vascular cell adhesion molecule : Implications for its mode of action in multiple sclerosis. / Graber, J.; Zhan, M.; Ford, D.; Kursch, F.; Francis, G.; Bever, C.; Panitch, H.; Calabresi, P. A.; Dhib-Jalbut, S.

In: Journal of Neuroimmunology, Vol. 161, No. 1-2, 04.2005, p. 169-176.

Research output: Contribution to journalArticle

Graber, J, Zhan, M, Ford, D, Kursch, F, Francis, G, Bever, C, Panitch, H, Calabresi, PA & Dhib-Jalbut, S 2005, 'Interferon-β-1a induces increases in vascular cell adhesion molecule: Implications for its mode of action in multiple sclerosis', Journal of Neuroimmunology, vol. 161, no. 1-2, pp. 169-176. https://doi.org/10.1016/j.jneuroim.2004.11.017
Graber, J. ; Zhan, M. ; Ford, D. ; Kursch, F. ; Francis, G. ; Bever, C. ; Panitch, H. ; Calabresi, P. A. ; Dhib-Jalbut, S. / Interferon-β-1a induces increases in vascular cell adhesion molecule : Implications for its mode of action in multiple sclerosis. In: Journal of Neuroimmunology. 2005 ; Vol. 161, No. 1-2. pp. 169-176.
@article{3b5aaadc38aa4283b63bef3123c35227,
title = "Interferon-β-1a induces increases in vascular cell adhesion molecule: Implications for its mode of action in multiple sclerosis",
abstract = "We investigated soluble vascular cell adhesion molecule-1 (sVCAM) levels and MRI lesions over 24 weeks in 15 Relapsing Remitting MS (RRMS) patients randomized prospectively to receive once-weekly (qw) IFN-β-1a 30 μg intramuscularly (IM) (Group I, 8 patients) or three-times-weekly (tiw) IFN-β-1a 44 μg subcutaneously (SC) (Group II, 7 patients). Both groups demonstrated a significant increase in sVCAM during treatment when compared to pre-treatment levels. Patients on IFN-β-1a 44 μg SC tiw had a significant (p<0.0001) mean increase in sVCAM of 321.9 ng/ml which was significantly greater (p<0.0001) than with IFN-β-1a 30 μg IM qw (68.6 ng/ml). There was a negative correlation between combined unique (CU) MRI lesions and sVCAM levels within the IFN-β-1a 44 μg SC tiw group (slope=-0.00106, p=0.009). We postulate that the mode of action of IFN-β therapy in MS may involve the induction of an increase in sVCAM. sVCAM could bind VLA-4 on T-cells and intercept their adhesion to the blood brain barrier (BBB). This mechanism is consistent with the observed clinical effect of IFN-β in reducing MRI contrast enhancing lesions.",
keywords = "Interferon-beta (IFN-β-1a), Multiple sclerosis, Vascular cell adhesion molecule (VCAM), Very late antigen-4 (VLA-4)",
author = "J. Graber and M. Zhan and D. Ford and F. Kursch and G. Francis and C. Bever and H. Panitch and Calabresi, {P. A.} and S. Dhib-Jalbut",
year = "2005",
month = "4",
doi = "10.1016/j.jneuroim.2004.11.017",
language = "English (US)",
volume = "161",
pages = "169--176",
journal = "Journal of Neuroimmunology",
issn = "0165-5728",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Interferon-β-1a induces increases in vascular cell adhesion molecule

T2 - Implications for its mode of action in multiple sclerosis

AU - Graber, J.

AU - Zhan, M.

AU - Ford, D.

AU - Kursch, F.

AU - Francis, G.

AU - Bever, C.

AU - Panitch, H.

AU - Calabresi, P. A.

AU - Dhib-Jalbut, S.

PY - 2005/4

Y1 - 2005/4

N2 - We investigated soluble vascular cell adhesion molecule-1 (sVCAM) levels and MRI lesions over 24 weeks in 15 Relapsing Remitting MS (RRMS) patients randomized prospectively to receive once-weekly (qw) IFN-β-1a 30 μg intramuscularly (IM) (Group I, 8 patients) or three-times-weekly (tiw) IFN-β-1a 44 μg subcutaneously (SC) (Group II, 7 patients). Both groups demonstrated a significant increase in sVCAM during treatment when compared to pre-treatment levels. Patients on IFN-β-1a 44 μg SC tiw had a significant (p<0.0001) mean increase in sVCAM of 321.9 ng/ml which was significantly greater (p<0.0001) than with IFN-β-1a 30 μg IM qw (68.6 ng/ml). There was a negative correlation between combined unique (CU) MRI lesions and sVCAM levels within the IFN-β-1a 44 μg SC tiw group (slope=-0.00106, p=0.009). We postulate that the mode of action of IFN-β therapy in MS may involve the induction of an increase in sVCAM. sVCAM could bind VLA-4 on T-cells and intercept their adhesion to the blood brain barrier (BBB). This mechanism is consistent with the observed clinical effect of IFN-β in reducing MRI contrast enhancing lesions.

AB - We investigated soluble vascular cell adhesion molecule-1 (sVCAM) levels and MRI lesions over 24 weeks in 15 Relapsing Remitting MS (RRMS) patients randomized prospectively to receive once-weekly (qw) IFN-β-1a 30 μg intramuscularly (IM) (Group I, 8 patients) or three-times-weekly (tiw) IFN-β-1a 44 μg subcutaneously (SC) (Group II, 7 patients). Both groups demonstrated a significant increase in sVCAM during treatment when compared to pre-treatment levels. Patients on IFN-β-1a 44 μg SC tiw had a significant (p<0.0001) mean increase in sVCAM of 321.9 ng/ml which was significantly greater (p<0.0001) than with IFN-β-1a 30 μg IM qw (68.6 ng/ml). There was a negative correlation between combined unique (CU) MRI lesions and sVCAM levels within the IFN-β-1a 44 μg SC tiw group (slope=-0.00106, p=0.009). We postulate that the mode of action of IFN-β therapy in MS may involve the induction of an increase in sVCAM. sVCAM could bind VLA-4 on T-cells and intercept their adhesion to the blood brain barrier (BBB). This mechanism is consistent with the observed clinical effect of IFN-β in reducing MRI contrast enhancing lesions.

KW - Interferon-beta (IFN-β-1a)

KW - Multiple sclerosis

KW - Vascular cell adhesion molecule (VCAM)

KW - Very late antigen-4 (VLA-4)

UR - http://www.scopus.com/inward/record.url?scp=14844297366&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14844297366&partnerID=8YFLogxK

U2 - 10.1016/j.jneuroim.2004.11.017

DO - 10.1016/j.jneuroim.2004.11.017

M3 - Article

VL - 161

SP - 169

EP - 176

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

IS - 1-2

ER -