Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis

Lipoic acid (LA) suppresses and treats murine experimental autoimmune encephalomyelitis (EAE), which models multiple sclerosis. However, the mechanisms by which LA mediates its effects in EAE are only partially known. In the present study, LA (25, 50 and 100 mu g/ml) inhibited upregulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-alpha (TNF-alpha) stimulated cultured brain endothelial cells. Immunohistochemical analysis of spinal cords from SJL mice that had received LA (100 mg/kg/day) following immunization to induce EAE exhibited markedly reduced expression of ICAM-1 and VCAM-1 compared with that of EAE mice receiving saline. Co-localization analysis showed that TCAM-1 and VCAM-1 expression increased over endothelial cells (staining positive for von Willebrand factor, vWF) in EAE and that LA decreased the expression levels to that observed in naive mice. Spinal cords from mice receiving LA had significantly reduced inflammation (decreased CD4 and CD11b staining) as compared to EAE mice that received saline. Overall, our data suggest that the anti-inflammatory effects of LA in EAE may be partly due to inhibition of ICAM-I and VCAM-1 expression by central nervous system (CNS) endothelial cells. (c) 2006 Elsevier B.V. All rights reserved.