J Neuroimmunol. 2004 Mar;148(1-2):146-53
Morini M, Roccatagliata L, Dell'Eva R, Pedemonte E, Furlan R, Minghelli S, Giunti D, Pfeffer U, Marchese M, Noonan D, Mancardi G, Albini A, Uccelli A.
Molecular Oncology Laboratory, National Cancer Research Institute, Genoa, Italy.
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.