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

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