Effects of the novel immunosuppressant FTY720 in a murine rheumatoid arthritis model.
We investigated the effects and mechanisms by which FTY720 (FTY) inhibits arthritis development in the SKG mouse rheumatoid arthritis (RA) model. FTY (1mg/kg/day) administration suppressed the progression of laminarin-induced arthritis in SKG mice. FTY treatment decreased IL-6 and TNF-alpha expression in synovial fibroblast cells and the number of inflammatory cells overall. Bone destruction was also suppressed by treatment with FTY. The numbers of CD4(+) and CD8(+) T cells were significantly increased in the thymus and decreased in the spleen in FTY-treated SKG mice. FTY enhanced IL-4 production by CD4(+) T cells stimulated by allogeneic spleen cells and inhibited prostaglandin E(2) (PGE(2)) production by a TNF-alpha-stimulated synovial fibroblast cell line. These results indicate that FTY can inhibit arthritis in SKG mice via sequestration of autoimmune CD4(+) T cells in the thymus, enhancement of Th2 immune responses, and inhibition of PGE(2) production by synovial cells.
Tsunemi
Sachi
S
Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Iwasaki
Tsuyoshi
T
Kitano
Sachie
S
Imado
Takehito
T
Miyazawa
Keiji
K
Sano
Hajime
H
D000284:Administration, Oral; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D000068876:Fingolimod Hydrochloride; D005936:Glucans; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D011134:Polysaccharides; D011409:Propylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology
D016207:Cytokines; D005936:Glucans; D007166:Immunosuppressive Agents; D011134:Polysaccharides; D011409:Propylene Glycols; D015847:Interleukin-4; C008247:laminaran; D000068876:Fingolimod Hydrochloride; D015232:Dinoprostone; D013110:Sphingosine