Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis

Gail Marracci, Richard E. Jones, Gabriel P. McKeon, Dennis Bourdette

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Oxidative injury may be important to the pathogenesis of multiple sclerosis (MS). We tested the antioxidant alpha lipoic acid (ALA) in an experimental murine model of MS, experimental autoimmune encephalomyelitis (EAE). ALA was administered to SJL mice 7 days after immunization with proteolipid protein (PLP) 139-151 peptide. Mice that received 5-100 mg/kg/day of ALA had dose-dependent reductions in their 10-Day Cumulative Disease Scores (10-Day CDS) by 23-100%. Minimal inflammation, demyelination and axonal loss occurred in the spinal cords (SC) of ALA-suppressed mice, and there was a marked reduction in CD3+ T cells and CD11b+ monocyte/macrophage cells within the SC. Mice treated with ALA (100 mg/kg/day) commencing on the first day of clinical EAE had a significant reduction in 10-Day CDS. SC of ALA-treated mice had reduced demyelination and axonal loss and a rapid reduction in CD3+ T cells. In vitro, ALA and its reduced form, dihydrolipoic acid, inhibited the activity of matrix metalloproteinase-9 (MMP-9) in a dose-dependent fashion. ALA is highly effective at suppressing and treating EAE and does so by inhibiting T cell trafficking into the SC, perhaps by acting as a matrix metalloproteinase inhibitor.

Original languageEnglish (US)
Pages (from-to)104-114
Number of pages11
JournalJournal of Neuroimmunology
Volume131
Issue number1-2
DOIs
StatePublished - Oct 2002

Fingerprint

Thioctic Acid
Autoimmune Experimental Encephalomyelitis
Cell Movement
Spinal Cord
T-Lymphocytes
Demyelinating Diseases
Multiple Sclerosis
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 9
Monocytes
Immunization
Theoretical Models
Antioxidants
Macrophages
Inflammation
Peptides
Wounds and Injuries

Keywords

  • Alpha lipoic acid
  • EAE
  • Matrix metalloproteinase
  • MMP inhibitor
  • Multiple sclerosis

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. / Marracci, Gail; Jones, Richard E.; McKeon, Gabriel P.; Bourdette, Dennis.

In: Journal of Neuroimmunology, Vol. 131, No. 1-2, 10.2002, p. 104-114.

Research output: Contribution to journalArticle

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