Abstract
Experimental autoimmune neuritis (EAN) is a T cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system and an animal model of human inflammatory demyelinating polyradiculoneuropathy. AUY954, which targets selectively the sphingosine-1-phosphate receptor 1 (S1P(1)), is known to sequester lymphocytes into secondary lymphoid tissues. In EAN rats, AUY954 greatly prevented paraparesis if administrated from the day of immunization. T cell, B cell, and macrophage infiltration, inflammatory demyelination, and local expression of interleukine-17 and matrix metalloproteinase-9 in sciatic nerves of EAN rats were significantly decreased by AUY954 treatment. Therefore, S1P(1) modulation might be a potential treatment option for inflammatory neuropathies.
MeSH terms
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Animals
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology
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Chemotaxis, Leukocyte / drug effects
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Chemotaxis, Leukocyte / immunology
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Disease Models, Animal
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Guillain-Barre Syndrome / drug therapy*
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Guillain-Barre Syndrome / immunology
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Guillain-Barre Syndrome / metabolism
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Immunologic Factors / pharmacology
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Immunologic Factors / therapeutic use
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Interleukin-17 / metabolism
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Macrophages / drug effects
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Macrophages / immunology
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Male
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Matrix Metalloproteinase 9 / metabolism
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Neuritis, Autoimmune, Experimental / drug therapy*
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Neuritis, Autoimmune, Experimental / immunology
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Neuritis, Autoimmune, Experimental / metabolism
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Paraparesis / drug therapy
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Paraparesis / immunology
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Paraparesis / prevention & control
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Rats
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Rats, Inbred Lew
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Receptors, Lysosphingolipid / drug effects*
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Receptors, Lysosphingolipid / metabolism
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Sciatic Nerve / drug effects
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Sciatic Nerve / immunology
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Sciatic Nerve / metabolism
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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Thiophenes / pharmacology*
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Thiophenes / therapeutic use
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Treatment Outcome
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beta-Alanine / analogs & derivatives*
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beta-Alanine / pharmacology
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beta-Alanine / therapeutic use
Substances
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AUY 954
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Immunologic Factors
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Interleukin-17
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Receptors, Lysosphingolipid
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Thiophenes
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beta-Alanine
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Matrix Metalloproteinase 9