AUY954, a selective S1P(1) modulator, prevents experimental autoimmune neuritis.
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.
Zhang
Zhi-Yuan
ZY
Institute of Brain Research, University of Tuebingen, Tuebingen, Germany.
Zhang
Zhiren
Z
Zug
Caroline
C
Nuesslein-Hildesheim
Barbara
B
Leppert
David
D
Schluesener
Hermann J
HJ
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D020275:Guillain-Barre Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D020381:Interleukin-17 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D020335:Paraparesis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew; D049349:Receptors, Lysosphingolipid / Q000187:drug effects* / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
C517408:AUY 954; D007155:Immunologic Factors; D020381:Interleukin-17; D049349:Receptors, Lysosphingolipid; D013876:Thiophenes; D015091:beta-Alanine; D020780:Matrix Metalloproteinase 9