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.
N1 - Funding Information:
This study was supported by grants from Serono Incorporated, The National Institute of Neurological Disorders and Stroke (K-24-NS02082)(Dr. Dhib-Jalbut), the Department of Veteran's Affairs MS Center of Excellence-East (Drs. Dhib-Jalbut and Bever), and USPHS training grant HL07612-15 provided through the University of Maryland at Baltimore School of Medicine, Office of Student Research (J Graber). The authors also wish to thank Rameeza Allie, Man Chen, and Tapas Makar for their technical assistance, and Dr. Jordan Warnick for his mentorship.
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)
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U2 - 10.1016/j.jneuroim.2004.11.017
DO - 10.1016/j.jneuroim.2004.11.017
M3 - Article
C2 - 15748956
AN - SCOPUS:14844297366
SN - 0165-5728
VL - 161
SP - 169
EP - 176
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -