Suppression of encephalitogenic T-cell responses by cilostazol is associated with upregulation of regulatory T cells.
Cilostazol is a specific phosphodiesterase III inhibitor. Recent data show that cilostazol has anti-inflammatory effects and administration of cilostazol ameliorates experimental autoimmune encephalomyelitis (EAE). In this study, we used a mouse EAE model to explore the role of cilostazol in Th1 and Th17 cell-mediated immune responses. We found that cilostazol suppressed mitogen or antigen-induced T-cell responses and Th17 cell differentiation in vitro, which correlated with enhanced Treg-cell responses. Beginning of oral administration of cilostazol at the onset of EAE significantly inhibited encephalitogenic T cells, reduced the levels of inflammatory cytokines in the central nervous system, and ameliorated the severity of EAE. Moreover, administration of cilostazol markedly enhanced Treg-cell response in vivo. Cilostazol, therefore, may exert its therapeutic effects through upregulation of Treg-cell activity.
Wang
Shouli
S
Department of Cardiology, Cardiovascular Research Institute, Shenyang Northern Hospital, Shenyang, Liaoning 110840, China.
Yan
Chenghui
C
Xu
Hui
H
Zhao
Xin
X
Han
Yaling
Y
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000077407:Cilostazol; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D058987:Phosphodiesterase 3 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D016896:Treatment Outcome
D000941:Antigens; D016207:Cytokines; D058987:Phosphodiesterase 3 Inhibitors; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol