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

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.

Resistance to experimental autoimmune encephalomyelitis development in Lewis rats from a conventional animal facility

“…The severity of histologic neural tissue lesions clearly correlated with these clinical symptoms. Cervical spinal cord sections showed typical and abundant inflammatory foci, localized around small vessels, similar to many research reports (Stanislaus et al 2001). Differing from these results, animals from Botucatu colony immunized in similar conditions, displayed a very low susceptibility to EAE development.…”

Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

“…We expected a decrease in the level of inflammatory infiltration during the remission phase because established data have shown that inflammatory cells strongly contribute to the pathology of this disease (Man et al 2007). In addition, experimental therapeutic strategies have demonstrated a clear correlation between clinical remission and the prevention of mononuclear cell transmigration to the spinal cord (Stanislaus et al 2001). Encephalitogenic T cells undergo apoptosis during the remission phase, which may lead to a decrease in inflammatory infiltrate with- Fig.…”

Therapeutic potential of lovastatin in multiple sclerosis

“…In particular, lovastatin has been shown to inhibit the induction of inducible nitric oxide synthase and proinflammatory cytokines in rat astrocytes, microglia and macrophages [2] and to repress MHC-II mediated T-cell activation [3]. Moreover, lovastatin treatment decreased neuroinflammatory activity and clinical signs in experimental allergic encephalomyelitis, an animal model for multiple sclerosis (MS) [4]. On the basis of these findings we have begun to investigate whether lovastatin could be a treatment option for MS patients.…”