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

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.