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Recent studies have shown that autophagy is involved in peripheral nervous system disease. However, the role of autophagy in the pathogenesis of experimental autoimmune neuritis (EAN) remains unclear. Therefore, EAN was induced by a subcutaneous injection into both hind footpads of synthetic neuritogenic P2(57-81) peptide in male Lewis rats. The clinical evaluation was completed using a 10-point scale method. The histological alteration of sciatic nerves was analyzed by hematoxylin and eosin and luxol fast blue staining. The ultrastructure of sciatic nerves was analyzed by transmission electron microscopy. Expressions of beclin-1 and microtubule-associated protein light chain-3 (LC3) and p62/SQSTM1 were determined by western blot. 3-Methyladenine, the inhibitor of autophagy, was used in this research. Results showed that the clinical scores were significantly increased from day 6 to day 16 after immunization compared with the control group. Compared with the control group, the number of inflammatory cells and the histological score of sciatic nerves were significantly increased, expressions of beclin-1 and LC3-II and the ratio of LC3-II/LC3-I in the sciatic nerve were significantly increased, and the expression of p62 was significantly decreased in the EAN model group. Considerable double-membrane autophagosomes in axons and myelin sheaths of sciatic nerves were observed and the number of autophagosomes in axons and myelin sheaths of sciatic nerves in the EAN model group was obviously increased compared with the control group. 3-Methyladenine ameliorated the neurologic severity of EAN. Our results suggest that autophagy activity in nerve tissue of EAN rats is increased, which may be associated with the pathogenesis of EAN.

Neuroimmune crosstalk in neuropathic pain is a key contributor to pain hypersensitivity following nervous system injury. CD4+CD25+Foxp3+ regulatory T cells (Tregs) are endogenous immune suppressors, reducing T-cell proliferation and proinflammatory cytokine production. Currently, the role of Tregs in neuropathic pain is unknown. In this study, we tested the effects of expanding Tregs on pain hypersensitivity and neuroinflammation in 2 models of neuropathy; sciatic nerve chronic constriction injury and experimental autoimmune neuritis in rats. Following chronic constriction injury, treatment with CD28 superagonist (CD28SupA), a Treg population expander, significantly increased Tregs in the lymphoid tissues, injured sciatic nerve, and lumbar spinal cord of rats. CD28SupA treatment led to a significant reduction in mechanical pain hypersensitivity, alongside a decrease in the numbers of infiltrating T cells, macrophages, and antigen-presenting cells in the sciatic nerve and dorsal root ganglia. In experimental autoimmune neuritis-affected rats, CD28SupA treatment resulted in a significant improvement in disease severity and in mechanical pain hypersensitivity. This was associated with a reduction in the numbers of T cells, macrophages, and antigen-presenting cells in the sciatic nerve and dorsal root ganglia, and reduced activation of microglia and infiltration of T cells in the spinal cord. Furthermore, depletion of Tregs by a CD25 antibody in mice with a partial sciatic nerve ligation resulted in prolonged mechanical pain hypersensitivity. These findings suggest that Tregs play a role in endogenous recovery from neuropathy-induced pain. Thus, this T-cell subset may be specifically targeted to alleviate chronic neuropathic pain.

Current knowledge about the pathogenic mechanisms involved in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) supports an autoimmune etiology. Some of the cell and humorally mediated immune responses that contribute to the development of CIDP resemble those implicated in multiple sclerosis (MS). The effector role of circulating antibodies has recently been revisited. In addition, similar to the situation in MS, histopathologic studies support the heterogeneity of disease mechanisms in CIDP, with variants showing axon damage. In addition to intravenous immunoglobulin (IVIg), prednisone, and plasma exchange, immunomodulatory drugs also were used to treat CIDP, although no definitive trial data are available. One class of immunomodulators, interferon beta formulations, has proven efficacy in the treatment of MS, and because of clinical similarities between the two diseases it is attractive to investigate whether some agents that are effective in the treatment of MS would also be effective in CIDP. Preliminary studies have evaluated the effects of interferon beta formulations in the treatment of CIDP, one of which has shown promising results and warrants further investigation.

PURPOSE OF REVIEW This article gives an overview on animal models for immune-mediated demyelinating disorders of the peripheral nervous system. As insight into human disease is mainly based on biopsy material and ex-vivo analysis, an understanding of the pathogenetic mechanism of these complex and heterogeneous disorders is mainly based on animal models. RECENT FINDINGS Besides experimental autoimmune neuritis in rats, recent efforts to establish this model in mice are discussed. In addition, models for spontaneous autoimmune neuropathies and secondary immune reactions in degenerative disorders of the peripheral nervous system are reviewed. SUMMARY Recently described animal models offer the possibility to analyse the complex interaction of genetic and immunological factors. The entire panel of animal models for immune-mediated disorders of the peripheral nervous system provides a rational basis for studying the mechanisms of pathogenesis and new immunotherapeutic strategies for human autoimmune demyelinating neuropathies.

The significance of immune reactions against peripheral nervous system antigens in the human inflammatory polyneuropathies is still uncertain. Using a very sensitive assay, we found greatly increased levels of anti-P2 antibodies in sera of animals with experimental allergic neuritis (EAN) but no increases in humans with acute Guillain-Barré syndrome (GBS), chronic relapsing polyneuritis (CRIP), axonal neuropathy, or normals. P2 protein and CNS basic protein did not induce any increased proliferation in lymphocytes of GBS or CRIP patients. We conclude that P2 and BP appear unlikely to be targets for humoral or cellular immune reactivity in GBS or CRIP.