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From bench to bedside—experimental rationale for immune-specific therapies in the inflamed peripheral nerve

Nature Clinical Practice Neurology volume 3, pages 198–211 (2007)Cite this article

Abstract

Guillain–Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy are autoimmune-mediated inflammatory diseases of the PNS. In recent years, substantial progress has been made towards understanding the immune mechanisms that underlie these conditions, in large part through the study of experimental models. Here, we review the available animal models that partially mimic human Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy, and discuss the wide range of therapeutic approaches that have been successfully established in these models of inflammatory neuropathies. Transfer of this preclinical knowledge to patients has been far less successful, and inflammatory neuropathies are still associated with significant morbidity and mortality. We will summarize successful therapeutic trials in human autoimmune neuropathies to provide a vantage point for the transfer of experimental treatment strategies to clinical practice in immune-mediated diseases of the peripheral nerve.

Key Points

  • Experimental autoimmune neuritis in animals models many aspects of human Guillain–Barré syndrome, an acute inflammatory neuropathy

  • Animal models of demyelinating and axonal Guillain–Barré syndrome subtypes differ in pathology and disease mechanism

  • Autoreactive T lymphocytes are key orchestrators of autoimmune neuropathies, whereas macrophages and humoral immune responses mediate local tissue damage

  • Successful therapeutic strategies in models of experimental autoimmune neuritis have targeted various stages of disease pathology

  • Transfer of experimental therapies to patients has shown limited success

  • Plasma exchange and intravenous immunoglobulin remain the therapeutic mainstays in acute autoimmune neuropathies at present

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Figure 1: Pathological mechanisms of inflammatory neuropathies

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Acknowledgements

This work was supported by grants from the German Research Foundation (GRK320) and the Research Commission of the Heinrich-Heine University of Düsseldorf (FoKo; to BC Kieseier and G Meyer zu Hörste).

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  1. all at the Department of Neurology, G Meyer zu Hörste is a Resident Neurologist, H-P Hartung is Professor and Chair, and BC Kieseier is a Professor of Neurology, Heinrich-Heine University of Düsseldorf, Düsseldorf, Germany.,

    Gerd Meyer zu Hörste, Hans-Peter Hartung & Bernd C Kieseier

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  1. Gerd Meyer zu Hörste
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  2. Hans-Peter Hartung
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  3. Bernd C Kieseier
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Correspondence to Bernd C Kieseier.

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Supplementary information

Supplementary Table 1

Complete overview of published therapeutic approaches in experimental autoimmune neuritis. (DOC 117 kb)

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Meyer zu Hörste, G., Hartung, HP. & Kieseier, B. From bench to bedside—experimental rationale for immune-specific therapies in the inflamed peripheral nerve. Nat Rev Neurol 3, 198–211 (2007). https://doi.org/10.1038/ncpneuro0452

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