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)
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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
VL - 161
SP - 169
EP - 176
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
SN - 0165-5728
IS - 1-2
ER -