Selective phosphodiesterase-3 inhibitor cilostazol ameliorates experimental autoimmune encephalomyelitis.
We investigated the possible therapeutic effect of cilostazol, a specific inhibitor of phosphodiesterase-3, for experimental autoimmune encephalomyelitis (EAE). Mice affected with EAE induced by inoculation with MOG(35-55) were fed with cilostazol or vehicle control. The clinical EAE scores of the cilostazol-fed mice were lower than those of the controls. Serum level of soluble intercellular adhesion molecule-1 was significantly lower in the cilostazol-fed mice than in the controls. In the recall responses with MOG(35-55), proliferation and IFN-gamma production by lymphocytes from cilostazol-fed mice were significantly reduced. Cilostazol may exhibit repressive effects on EAE by reducing the antigen-specific T-cell response and decreasing the expression of the adhesion molecules. Cilostazol is a hopeful choice for the treatment of multiple sclerosis.
Kureshiro
Juri
J
Department of Neurology, Kinki University School of Medicine, Ohno-higashi, Osaka-Sayama, Osaka, Japan.
Miyamoto
Katsuichi
K
Tanaka
Noriko
N
Kusunoki
Susumu
S
D000818:Animals; D000077407:Cilostazol; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D006023:Glycoproteins / Q000633:toxicity; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy*; D063308:Myelin-Oligodendrocyte Glycoprotein; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000633:toxicity; D058987:Phosphodiesterase 3 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D006023:Glycoproteins; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D019007:P-Selectin; D010446:Peptide Fragments; D058987:Phosphodiesterase 3 Inhibitors; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C445081:myelin oligodendrocyte glycoprotein (35-55); D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D007371:Interferon-gamma; D000077407:Cilostazol