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

J Neuroimmunol. 2004 Mar;148(1-2):146-53. doi: 10.1016/j.jneuroim.2003.11.021.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antioxidants / therapeutic use*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Female
  • Fibrosarcoma / drug therapy
  • Glycoproteins
  • Immunization
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Spinal Cord / drug effects
  • Spinal Cord / pathology
  • T-Lymphocytes / drug effects
  • Thioctic Acid / therapeutic use*


  • Antioxidants
  • Glycoproteins
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)
  • Interleukin-4
  • Thioctic Acid
  • Interferon-gamma
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9