Animal models of chronic inflammatory demyelinating polyneuropathy

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by a relapsing or chronic progressive course and immune‐mediating pathogenesis targeting the peripheral nervous system. The prevalence rate of CIDP is 1.6 to eight cases per 100 000 people, and the disorder is predominant among males. Immune‐modulating therapies, such as intravenous immunoglobulin, corticosteroids and plasmapheresis, are equally effective in classical CIDP. However, the pathogenesis of CIDP is heterogeneous, and atypical variants have been recognized as poor or non‐responders to these therapeutic approaches. For example, immunoglobulin G4 autoantibodies targeting paranodal molecules (neurofascin‐155, contactin‐1 and Caspr‐1) are thought to be involved in patients with unique findings (distal dominant and sensory ataxia with postural tremor, and non‐responders to intravenous immunoglobulin). Thus, it is necessary to decompose each immunological background to develop novel therapeutic approaches. Importantly, animal models for immune‐mediated neuropathies have provided substantial information about autoimmune mechanisms. The traditional experimental autoimmune neuritis model of acute inflammatory demyelinating polyneuropathy and a recent variety of spontaneous autoimmune polyneuropathy models based on non‐obese diabetes mice have provided valuable knowledge about the chronicity of immunopathogenesis. Here, we describe the representative subtypes of CIDP and their presumed pathogenesis, and discuss animal models that could extend understanding of this diversity.

Risk of osteoporosis in patients with chronic inflammatory neuropathy- a population-based cohort study

“…Chronic inflammation in these diseases is thought to promote bone loss through pro-inflammatory cytokines by inhibiting osteoblast activity and promoting osteoclast activity 41,42 . Interleukin-17 is one of the proinflammatory cytokines that contributes to bone loss 43 , and interleukin-17 levels were found to be high in both active CIDP patients and in an animal model of CIDP 44,45 . In addition, tumor necrosis factor alpha (TNF-α), which is known to induce osteoclastogenesis, plays a main role in animal models of autoimmune neuropathy, and autoimmune neuritis was attenuated in TNF-α knockout mice, probably by altering the balance between proinflammatory and anti-inflammatory macrophages 46–48 .…”

Recent advances in experimental approaches to immune‐mediated neuropathy

“…In addition, progress in the development of models of chronic or relapsing–remitting demyelinating neuropathy will facilitate therapeutic research. In this issue, Iijima provides a comprehensive review of the development of experimental models of CIDP, focused on the pathogenesis of CIDP and animal models characterized by chronic or relapsing–remitting deterioration …”