No abstract

Mononuclear cell infiltration into the CNS and induction of inflammatory cytokines and iNOS in diseases like multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE) have been implicated in subsequent disease pathogenesis and progression. We report that Lovastatin treatment blocks the clinical disease and induction of inflammatory cytokines and iNOS in spinal 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 cord. The data presented here documents that Lovastatin treatment attenuates the transmigration of mononuclear cells possibly by down regulating the expression 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 the histological changes and clinical signs and thus ameliorating the disease. These observations indicate that Lovastatin treatment may be of therapeutic value against inflammatory disease process associated with infiltration of activated mononuclear cells into the tissue.

The attenuation of experimental autoimmune encephalomyelitis (EAE) by Lovastatin (LOV) has now been well established. The present study was designed to explore the global effect of LOV treatment on expression of immune-related genes in lumbar spinal cord (LSC) during acute EAE by using Affymetrix DNA microarrays. LOV treatment demonstrated the limited infiltration of inflammatory cells into the LSC, and microarray analysis further validated those interpretations by demonstrating relatively less alteration in expression of immune response genes in LOV-treated EAE rats on peak clinical day and recovery vs. untreated EAE counterparts. There was significant change in expression of about 158 immune-related genes (including 127 genes reported earlier) in LOV-treated vs. untreated EAE (>1.5 or <-1.5 fold change; P

No abstract