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

Neuropharmacology. 2002 Apr;42(5):731-9. doi: 10.1016/s0028-3908(02)00015-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use*
  • Animals
  • Cell Movement / drug effects*
  • Cell Movement / immunology
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Immunologic
  • Hydroxyquinolines / chemistry
  • Hydroxyquinolines / pharmacology
  • Hydroxyquinolines / therapeutic use*
  • Injections, Subcutaneous
  • Interferon-gamma / biosynthesis
  • Male
  • Neuritis, Autoimmune, Experimental / immunology
  • Neuritis, Autoimmune, Experimental / pathology
  • Neuritis, Autoimmune, Experimental / prevention & control*
  • Peripheral Nerves / drug effects
  • Peripheral Nerves / immunology*
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / pathology*
  • Quinolones
  • Rats
  • Rats, Inbred Lew
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Adjuvants, Immunologic
  • Hydroxyquinolines
  • Quinolones
  • Tumor Necrosis Factor-alpha
  • roquinimex
  • Interferon-gamma
  • laquinimod