Anti-adhesion molecule therapy in Theiler's murine encephalomyelitis virus-induced demyelinating disease

Atsushi Inoue, Chang Sung Koh*, Masashi Yamazaki, Motoki Ichikawa, Mitsuaki Isobe, Yoshihiro Ishihara, Hideo Yagita, Byung S. Kim

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

We examined the role of leukocyte function-associated antigen (LFA)-1 and its counter-receptor intercellular adhesion molecule (ICAM)-1, one of the most important pairs of adhesion molecules, in the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Immunohistochemical study showed hyper-expression of ICAM-1 on vascular endothelial cells and expression of LFA-1 on mononuclear infiltrating cells in the spinal cords of TMEV-infected mice. Treatment with mAb to ICAM-1 and/or LFA-1 molecules resulted in significant suppression of the development of demyelinating disease, both clinically and histologically, with down-regulation in the CNS of the respective adhesion molecules after treatment. In mice treated with these mAb, the specific delayed-type hypersensitivity and T cell proliferative responses for TMEV were decreased. The production of tumor necrosis factor-α and IFN-γ in spleen cells was also decreased, but IL-4 production remained unchanged. These data suggest that ICAM-1/LFA-1 interaction is critically involved in the pathogenesis of TMEV-IDD and that antibodies to these adhesion molecules could be a novel therapeutic approach to the treatment of demyelinating diseases such as human multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)1837-1847
Number of pages11
JournalInternational Immunology
Volume9
Issue number12
DOIs
StatePublished - 1997

Keywords

  • Adhesion molecule
  • Demyelination
  • ICAM-1
  • LFA-1
  • Multiple sclerosis
  • Theiler's murine encephalomyelitis virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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