FTY720 ameliorates experimental autoimmune neuritis by inhibition of lymphocyte and monocyte infiltration into peripheral nerves.
Experimental autoimmune neuritis (EAN) is a T cell-mediated autoimmune demyelinating inflammatory disease of the peripheral nervous system (PNS). T cells and macrophages are essential for the initiation and development of EAN. FTY720 acts as an agonist of sphingosine-1-phosphate receptors, resulting in inhibition of lymphocyte egress from secondary lymphoid tissues and thymocytes from thymus. This investigation describes the immunosuppressive effects of FTY720 in EAN, the animal model of autoimmune neuropathies. FTY720 (1 mg/kg body weight) completely suppressed paraparesis if administrated from the day of immunization. Furthermore, FTY720 greatly reduced the severity and duration of EAN even when administrated after the appearance of the first neurological sign. T cell, B cell, and macrophage infiltration and demyelination of sciatic nerves were significantly decreased in FTY720-treated EAN. Therefore, FTY720 might be a potential candidate for treatment of inflammatory neuropathies.
Zhang
Zhiren
Z
Institute of Brain Research, University of Tuebingen, Calwer Street 3, D-72076 Tuebingen, Germany. zhangzhiren@yahoo.com
Zhang
Zhi-Yuan
ZY
Fauser
Uwe
U
Schluesener
Hermann J
HJ
D000818:Animals; D001835:Body Weight; D017252:CD3 Complex / Q000378:metabolism; D004195:Disease Models, Animal; D053331:Ectodysplasins / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D005434:Flow Cytometry / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D011409:Propylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000378:metabolism
D017252:CD3 Complex; D053331:Ectodysplasins; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D013449:Sulfonamides; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine