α-Lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis

Monica Morini, Luca Roccatagliata, Raffaella Dell'Eva, Enrico Pedemonte, Roberto Furlan, Simona Minghelli, Debora Giunti, Ulrich Pfeffer, Monica Marchese, Douglas Noonan, Gianluigi Mancardi, Adriana Albini, Antonio Uccelli

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)146-153
Number of pages8
JournalJournal of Neuroimmunology
Volume148
Issue number1-2
DOIs
Publication statusPublished - Mar 2004

Keywords

  • Anti-oxidant
  • Experimental autoimmune encephalomyelitis
  • Inflammation
  • Invasion
  • Multiple sclerosis

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

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