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.