Title
Soluble vascular cell adhesion molecule (VCAM) is associated with treatment effects of Interferon beta-1b in patients with Secondary Progressive Multiple Sclerosis
Author
Rieckmann, P.
Kruse, N.
Nagelkerken, L.
Beckmann, K.
Miller, D.
Polman, C.
Dahlke, F.
Toyka, K.V.
Hartung, H.P.
Stürzebecher, S.
TNO Preventie en Gezondheid
Publication year
2005
Abstract
Background: Subcutaneous IFNβ-1b (Betaferon®) is an established immunomodulatory treatment for relapsing remitting MS and active secondary progressive multiple sclerosis (SPMS). It modulates cytokine and adhesion molecule expression but long term in vivo effects of IFNβ-1b on the immune system are not known in multiple sclerosis. Objective: To address the effects of IFNβ-1b on serum levels for soluble adhesion molecules and cytokine receptors from MS patients. Methods: Serial blood samples were obtained from 40 patients of the frequent MRI subgroup (20 patients each from the placebo and the IFNβ-1b treatment group), participating in the European multi-center clinical trial with IFNβ-1b for secondary progressive MS, at regular intervals for up to 36 months. Soluble adhesion molecules (sVCAM, sICAM-1, sL-Selectin) as well as TNF-receptor I and II were analysed in the serum of patients by enzyme linked immunosorbent assays (ELISAs). Monthly brain MRI was performed in 34 of these patients (16 patients from the placebo and 18 from the IFNβ-1b group) during months 1-6 and 19-24 to monitor disease activity as assessed by newly occurring gadolinium (Gd) enhancing lesions. Results: An early and significant increase in sVCAM and sTNF-RII serum levels was detected in 16 out of 20 patients (80 %) treated with subcutaneous IFNβ-1b already at month 1 but was absent in all but one patient during placebo treatment (p<0.01). Raised sVCAM and TNF RII serum levels during months 1-6 inversely correlated with less MRI activity in the 19-24 months treatment interval in the IFNâ-1b treatment group ( p=0.0093 for TNF-RII; p=0.047 for VCAM). Conclusions: sVCAM and sTNF RII levels in the serum of SPMS patients are increased during IFNβ-1b therapy and may at least in part explain some of the treatment effects, like reduced immune cell transmigration. Chemicals / CAS: gadolinium, 7440-54-2; intercellular adhesion molecule 1, 126547-89-5; interferon beta serine, 90598-63-3; L selectin, 126880-86-2; interferon beta-1b, 145155-23-3; Interferon-beta, 77238-31-4; Vascular Cell Adhesion Molecule-1
Subject
Adhesion molecules
Cytolaine receptor
Interferon beta
Multiple sclerosis
Treatment effect
gadolinium
intercellular adhesion molecule 1
interferon beta serine
L selectin
placebo
tumor necrosis factor receptor 1
tumor necrosis factor receptor 2
blood sampling
cell adhesion
cell migration
clinical article
clinical trial
controlled clinical trial
controlled study
correlation analysis
disease activity
enzyme linked immunosorbent assay
Europe
frequency analysis
human
immunocompetent cell
nuclear magnetic resonance imaging
statistical significance
Adult
Double-Blind Method
Female
Humans
Interferon-beta
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis, Chronic Progressive
Statistics, Nonparametric
Vascular Cell Adhesion Molecule-1
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DOI
https://doi.org/10.1007/s00415-005-0681-7
TNO identifier
238454
ISSN
0340-5354
Source
Journal of Neurology, 252 (5), 526-533
Document type
article