Abstract
α-Lipoic acid (α-LA) is a neuroprotective metabolic antioxidant that has been shown to cross the blood brain barrier. We tested whether α-LA is capable to prevent MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). Daily oral administration of α-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 α-LA in a therapeutic protocol aimed at suppressing EAE after its onset. Intraperitoneal (i.p.), but not oral, administration of α-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 IFNγ and IL-4, suggesting an immunosuppressive activity on both Th1 and Th2 cytokines. In addition, α-LA inhibited the proteolytic activity of MMP2 and MMP9 only at very high doses. Our data indicate that α-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 α-LA as a potential therapy for MS.
Original language | English |
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Pages (from-to) | 146-153 |
Number of pages | 8 |
Journal | Journal of Neuroimmunology |
Volume | 148 |
Issue number | 1-2 |
DOIs | |
Publication status | Published - Mar 2004 |
Externally published | Yes |
Keywords
- Anti-oxidant
- Experimental autoimmune encephalomyelitis
- Inflammation
- Invasion
- Multiple sclerosis