Suppression of experimental autoimmune neuritis by ABR-215062 is associated with altered Th1/Th2 balance and inhibited migration of inflammatory cells into the peripheral nerve tissue

Autor(es): Zou L-P,Abbas N,Volkmann I,Nennesmo I,Levi M,Wahren B,Winblad B,Hedlund G,Zhu J

Resumo: The therapeutic effects of ABR-215062, which is a new immunoregulator derived from Linomide, have been evaluated in experimental autoimmune neuritis (EAN), a CD4(+) T cell-mediated animal model of Guillain-Barré syndrome in man. In previous studies, we reported that Linomide suppressed the clinical EAN and myelin antigen-reactive T and B cell responses. Here EAN induced in Lewis rats by inoculation with peripheral nerve myelin P0 protein peptide 180-199 and Freund's complete adjuvant was strongly suppressed by ABR-215062 administered daily subcutaneously from the day of inoculation. ABR-215062 dose-dependently reduced the incidence of EAN, ameliorated clinical signs and inhibited P0 peptide 180-199-specific T cell responses as well as also the decreased inflammation and demyelination in the peripheral nerves. The suppression of clinical EAN was associated with inhibition of the inflammatory cytokines IFN-gamma and TNF-alpha, as well as the enhancement of anti-inflammatory cytokine IL-4 in lymph node cells and periphery nerve tissues, respectively, in a dose-dependent manner. These effects indicate that ABR-215062 may mediate its effects by regulation of Th1/Th2 cytokine balance and suggest that ABR-215062 is potentially a new chemical entity for effective treatment of autoimmune diseases.

Palavras-Chave: Experimental autoimmnue neuritis; ABR-215062; Linomide; Guillain-Barré syndrome; Cytokines

Imprenta: Neuropharmacology, v. 42, n. 5, p. 731-739, 2002

Identificador do objeto digital: 10.1016/S0028-3908(02)00015-1

Descritores: Guillain-Barre Syndrome - Biosynthesis ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Cytopathology ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Protein synthesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Cytokines ; Guillain-Barre Syndrome - Inflammation ; Guillain-Barre Syndrome - Immunology

Data de publicação: 2002