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Soluble vascular cell adhesion molecule (VCAM) is associated with treatment effects of Interferon beta-1b in patients with Secondary Progressive Multiple Sclerosis

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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.

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Authors and Affiliations

  1. Neurologische Universitätsklinik Würzburg, Würzburg, Germany

    Peter Rieckmann MD, N. Kruse PhD & K. V. Toyka MD

  2. Clinical Research Unit for Multiple Sclerosis and Neuroimmunology, Dept. of Neurology—Julius Maximilians University, Josef-Schneider-Str. 11, 97080, Würzburg, Germany

    Peter Rieckmann MD

  3. TNO Prevention and Health, Leiden, The Netherlands

    L. Nagelkerken PhD

  4. Schering AG, Berlin, Germany

    K. Beckmann PhD, F. Dahlke MD & S. Stürzebecher MD

  5. National Hospital for Neurology and Neurosurgery, London, UK

    D. Miller MD

  6. Dept. of Neurology, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands

    C. Polman MD

  7. Neurologische Universitätsklinik, Düsseldorf, Germany

    H. P. Hartung MD

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  1. Peter Rieckmann MD
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  2. N. Kruse PhD
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  10. S. Stürzebecher MD
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Correspondence to Peter Rieckmann MD.

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Rieckmann, P., Kruse, N., Nagelkerken, L. et al. Soluble vascular cell adhesion molecule (VCAM) is associated with treatment effects of Interferon beta-1b in patients with Secondary Progressive Multiple Sclerosis. J Neurol 252, 526–533 (2005). https://doi.org/10.1007/s00415-005-0681-7

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  • DOI: https://doi.org/10.1007/s00415-005-0681-7

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