Lovastatin treatment decreases mononuclear cell infiltration into the CNS of Lewis rats with experimental allergic encephalomyelitis

Mononuclear cell infiltration into the CNS and induction of inflammatory cy tokines and NOS in diseases like multiple sclerosis (MS) and experimental a llergic encephalomyelitis (EAE) have been implicated in subsequent disease pathogenesis and progression. We report that Lovastatin treatment blocks th e clinical disease and induction of inflammatory cytokines; and NOS in spin al cords of MBP induced EAE rats. A significant number of the infiltrating cells in CNS were ED1+ cells of monocyte/macrophage lineage. To understand the mechanism of efficacy of Lovastatin against EAE, we examined the effect of Lovastatin on the transmigration of mononuclear cells into EAE spinal c ord. The data presented here documents that Lovastatin treatment attenuates the transmigration of mononuclear cells possibly by down regulating the ex pression of LFA-1, a ligand for ICAM, in endothelial-leukocyte interaction. These results indicate that Lovastatin treatment prevents infiltration by mononuclear cells into the CNS of rats induced for EAE, thereby lessening t he histological changes and clinical signs and thus ameliorating the diseas e. These observations indicate that Lovastatin treatment may be of therapeu tic value against inflammatory disease process associated with infiltration of activated mononuclear cells into the tissue. (C) 2001 Wiley-Liss, Inc.