Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis.
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.
Marracci
Gail H
GH
Department of Neurology, Oregon Health and Science University, Portland, OR 97201, USA.
Jones
Richard E
RE
McKeon
Gabriel P
GP
Bourdette
Dennis N
DN
D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D055502:Secondary Prevention; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D004791:Enzyme Inhibitors; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D008063:Thioctic Acid; D020780:Matrix Metalloproteinase 9