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J Neuroimmunol. 2004 Mar;148(1-2):146-53.

Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis.

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  • 1Molecular Oncology Laboratory, National Cancer Research Institute, Genoa, Italy.

Abstract

Alpha-lipoic acid (alpha-LA) is a neuroprotective metabolic antioxidant that has been shown to cross the blood brain barrier. We tested whether alpha-LA is capable to prevent MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). Daily oral administration of alpha-LA, starting at the time of immunization, significantly prevented EAE progression as compared to control mice. This was associated with a reduction of CNS infiltrating T cells and macrophages as well as decreased demyelination. We then tested alpha-LA in a therapeutic protocol aimed at suppressing EAE after its onset. Intraperitoneal (i.p.), but not oral, administration of alpha-LA significantly prevented disease progression when compared to vehicle-treated controls. Similarly, we observed significant reduction of demyelination and inflammatory infiltration. This clinical effect was not due to an impairment of MOG35-55 recognition by encephalitogenic T cells. In contrast, MOG-specific T cells showed a decreased production of IFNgamma and IL-4, suggesting an immunosuppressive activity on both Th1 and Th2 cytokines. In addition, alpha-LA inhibited the proteolytic activity of MMP2 and MMP9 only at very high doses. Our data indicate that alpha-LA can effectively interfere with the autoimmune reaction associated with EAE through mechanisms other than its antioxidant activity and supports further studies on the use of alpha-LA as a potential therapy for MS.

PMID:
14975595
[PubMed - indexed for MEDLINE]
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