Fingolimod phosphate promotes the neuroprotective effects of microglia

Fingolimod phosphate (FTY720) is a sphingosine 1-phosphate (S1P) receptor agonist that is being used as a new oral drug for multiple sclerosis. FTY720 prevents lymphocytes from moving out of the lymphoid organs and inhibits autoreactive lymphocytes from infiltrating the central nervous system. Whether FTY720 directly affects microglia-the innate immune cells of the central nervous system-is unclear. Here we show that FTY720 binds S1P(1) receptors to downregulate activated microglial production of such pro-inflammatory cytokines as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. FTY720 also upregulates microglial production of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor. These results suggested that FTY720 directly promotes the neuroprotective effects of microglia. Therefore, FTY720 may be a potent therapeutic agent for not only multiple sclerosis but also other neurologic diseases associated with microglial activation. (C) 2012 Elsevier B.V. All rights reserved.