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Immunopathogenesis and immunotherapy of multiple sclerosis

Nature Clinical Practice Neurology volume 2, pages 201–211 (2006)Cite this article

Abstract

Multiple sclerosis (MS) is a chronic disease of the CNS that is characterized by inflammation, demyelination and axonal injury. Although the etiology of MS is still unknown, many findings point toward a central role for the immune system in the pathogenesis of the disease. This hypothesis is strongly supported by the beneficial effects of immunomodulatory and immunosuppressive therapy on disease activity. Over the past few years, substantial progress has been made in deciphering the immune response in MS. Although animal models have advanced our knowledge of basic mechanisms of immune responses in the CNS, recent studies have also highlighted the differences between MS and its animal equivalent, experimental autoimmune encephalomyelitis. New immunotherapeutic agents have been developed and evaluated in clinical trials. Here, we review current knowledge of the immunopathogenesis of MS and corresponding animal models of disease, and discuss new immunointerventional treatment strategies based on changing pathogenetic concepts.

Key Points

  • The etiology of multiple sclerosis (MS) is unknown, but many findings indicate a central role for the immune system in the disease pathogenesis, and both genes and environmental factors influence the risk of developing disease

  • The most extensively studied animal model of MS is experimental autoimmune encephalomyelitis, a T-cell-mediated inflammatory disease of the CNS with variable degrees of demyelination and axonal damage

  • Traditionally, MS has been considered primarily to be a T-cell-mediated disease, but the importance of B lymphocytes in the pathogenesis of MS is beginning to be appreciated

  • There are important differences between the pathology of MS in humans and EAE in animals, particularly with regard to the involvement of B cells and CD8+ T cells

  • Targeting of the immune response is the most widely used treatment approach for MS; strategies range from nonselective immunosuppression to highly specific immune intervention

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Figure 1: Immunopathogenesis of multiple sclerosis.
Figure 2: Immune intervention strategies currently used or in development for the treatment of multiple sclerosis.

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Acknowledgements

B Hemmer, S Nessler and D Zhou were supported by grants from the Deutsche Forschungs-gemeinschaft, the Gemeinnützige Hertie-Stiftung and the German MS Society.

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Authors and Affiliations

  1. a professor of neurology Department of Neurology, at the Department of Neurology, Heinrich Heine University, Düsseldorf, Germany

    Bernhard Hemmer

  2. a trainee neurologist Department of Neurology, at the Department of Neurology, Heinrich Heine University, Düsseldorf, Germany

    Stefan Nessler

  3. a research fellow Department of Neurology, at the Department of Neurology, Heinrich Heine University, Düsseldorf, Germany

    Dun Zhou

  4. a professor of neurology Department of Neurology, at the Department of Neurology, Heinrich Heine University, Düsseldorf, Germany

    Bernd Kieseier

  5. Professor and Chair of Department of Neurology, at the Department of Neurology, Heinrich Heine University, Düsseldorf, Germany

    Hans-Peter Hartung

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Correspondence to Bernhard Hemmer.

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Competing interests

S Nessler and D Zhou declared they have no competing interests.

Bernhard Hemmer has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Biogen Idec, Sanofi-Aventis, Schering, Serono, Teva Pharmaceuticals, Wyeth and Amgen. Bernd Kieseier has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer, Biogen Idec, Sanofi-Aventis, Schering, Serono and Teva Pharmaceuticals. Hans-Peter Hartung has received honoraria for lectures and consulting from Bayer, Biogen Idec, Sanofi-Aventis, Schering, Serono, Teva Pharmaceuticals, Wyeth and Amgen.

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Hemmer, B., Nessler, S., Zhou, D. et al. Immunopathogenesis and immunotherapy of multiple sclerosis. Nat Rev Neurol 2, 201–211 (2006). https://doi.org/10.1038/ncpneuro0154

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