Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. 1245 42

Multiple Sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). We have shown that CNS-specific CD8 T cells (CNS-CD8) possess a disease suppressive function in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Previous studies have focused on the role of these cells predominantly in chronic models of disease, but the majority of MS patients present with a relapsing-remitting disease course. In this study, we evaluated the therapeutic role of CD8 T cells in the context of relapsing-remitting disease (RR-EAE), using SJL mice. We found that PLP178-191- and MBP84-104-CD8 ameliorated disease severity in an antigen-specific manner. In contrast, PLP139-151-CD8 did not suppress disease. PLP178-191-CD8 were able to reduce the number of relapses even when transferred during ongoing disease. We further ascertained that the suppressive subset of CD8 T cells was contained within the CD25+ CD8 T cell compartment post-in vitro activation with PLP178-191. Using Listeria monocytogenes (LM) encoding CNS antigens to preferentially prime suppressive CDS T cells in vivo, we show that LM infection induced disease suppressive CD8 T cells that protected and treated PLP178-191 disease. Importantly, a combination of PLP178-191-CDs transfer boosted by LM-PLP175-194 infection effectively treated ongoing disease induced by a non-cognate peptide (PLP139-151), indicating that this approach could be effective even in the context of epitope spreading. These data support a potential immunotherapeutic strategy using CD8 transfer and/or LM vaccination to boost disease regulatory CD8 T cells.
 ...
PMID:Therapeutic intervention in relapsing autoimmune demyelinating disease through induction of myelin-specific regulatory CD8 T cell responses. 3216 9