Treatment with P2 protein peptide 57-81 by nasal route is effective in Lewis rat experimental autoimmune neuritis

Autor(es): Zou L P,Zhu J,Deng G M,Levi M,Wahren B,Diab A,Hillert J,Link H


Resumo: Experimental autoimmune neuritis (EAN) is a CD4+ T cell-mediated autoimmune disorder of the peripheral nervous system (PNS) that can be actively induced in susceptible animal species and strains by active immunization with PNS myelin + Freund's complete adjuvant (FCA). EAN represents an animal model for studying the immunopathogenesis and treatment of Guillain-Barré syndrome (GBS), which is a major inflammatory demyelinating disease of the PNS in humans. Here, we report that treatment by nasal administration of the neuritogenic peptide 57-81 of the PNS myelin component, P2 protein, dose-dependently suppressed EAN severity and shortened clinical EAN. Clinical EAN relapse induced by rechallenge with BPM + FCA was also prevented in EAN rats receiving high dose P2 peptide. P2 peptide induced suppression of EAN was associated with PNS antigen specific T cell hyporesponsiveness reflected by lymphocyte proliferation, numbers of PNS antigen-reactive IFN-gamma secreting and IFN-gamma mRNA expressing lymph node cells, but elevated levels of PNS antigen reactive TGF-beta mRNA secreting cells. Reduced CD4+ T cell and macrophage infiltrations within the PNS were also observed. Based on these observations, nasal autoantigen administration should be further evaluated, considering its possible future use in GBS.


Palavras-Chave: Autoimmunity; ELISPOT; Experimental autoimmune neuritis (EAN); Guillain-Barré syndrome; Mocosal tolerance; P2-peptide


Imprenta: Journal of Neuroimmunology, v. 85, n. 2, p. 137-145, 1998


Identificador do objeto digital: 10.1016/S0165-5728(98)00022-8


Descritores: Guillain-Barre Syndrome - Biochemistry ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Cytopathology ; Guillain-Barre Syndrome - Molecular Structure ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - RNA ; Guillain-Barre Syndrome - Cytokines ; Guillain-Barre Syndrome - Molecular screening


Data de publicação: 1998