Fingolimod (FTY720), sphingosine 1-phosphate receptor modulator, shows superior efficacy as compared with interferon-β in mouse experimental autoimmune encephalomyelitis
Autor: | Kunio Sugahara, Atsushi Fukunari, Mamoru Koyama, Hirotoshi Kataoka, Noriyasu Seki, Takahisa Sugita, Kyoko Shimano, Kenji Chiba |
---|---|
Rok vydání: | 2011 |
Předmět: |
medicine.medical_specialty
Encephalomyelitis Autoimmune Experimental Lymphocyte Immunology Myelin oligodendrocyte glycoprotein Mice Subcutaneous injection Myelin Sphingosine immune system diseases Interferon hemic and lymphatic diseases Internal medicine medicine Animals Immunologic Factors Immunology and Allergy Myelin Proteolipid Protein Pharmacology Dose-Response Relationship Drug biology Fingolimod Hydrochloride Experimental autoimmune encephalomyelitis Interferon-beta medicine.disease Fingolimod nervous system diseases Myelin proteolipid protein Mice Inbred C57BL Endocrinology medicine.anatomical_structure Propylene Glycols biology.protein Female Immunosuppressive Agents medicine.drug |
Zdroj: | International Immunopharmacology. 11:366-372 |
ISSN: | 1567-5769 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |