Fingolimod (
FTY720), a
sphingosine 1-phosphate (
S1P) receptor modulator, inhibits S1P-dependent lymphocyte egress from secondary lymphoid organs and is highly effective in
experimental autoimmune encephalomyelitis (EAE) in mice. In this study, we directly compared the
therapeutic effects of
FTY720 and recombinant mouse
interferon (rm-IFN)-β on relapse and progression of EAE in mice. When
FTY720 at oral dose of 0.03 to 1 mg/kg was administered daily after establishment of EAE induced by
myelin proteolipid protein (PLP) in SJL/J mice, relapse of EAE was significantly inhibited during administration period.
Subcutaneous injection of rm-IFN-β (10,000 IU/mouse) also inhibited the relapse of EAE at early period; however EAE was relapsed in all the mice within administration period. Therapeutic administration of
FTY720 (0.03 to 1 mg/kg) significantly improved the symptoms of chronic EAE induced by
myelin oligodendrocyte glycoprotein in C57BL/6 mice whereas rm-IFN-β (10,000 IU/mouse) showed no clear effect. These results indicate that
FTY720 is more efficacious in mouse EAE as compared with rm-IFN-β.
FTY720 markedly reduced the frequency of PLP-specific Th17 and Th1 cells in the spinal cord of EAE mice. On the contrary,
FTY720 increased the frequency of PLP-specific Th17 and Th1 cells in the inguinal lymph nodes, suggesting inhibition of egress of myelin
antigen-specific Th cells from draining lymph nodes. From these results, the ameliorating effects of
FTY720 on EAE are likely due to reduction of infiltration of myelin
antigen-specific Th17 and Th1 cells into the central nervous system.