Effects of FTY720, a novel immunosuppressant, on experimental autoimmune uveoretinitis in rats.
The immunosuppressive properties of FTY720, a novel immunosuppressant obtained by structural modification of ISP-I isolated from the fermentation broth of Isaria sinclairii, were studied in experimental autoimmune uveoretinitis (EAU) in rats. Lewis rats were immunized with S-antigen and treated with FTY720 (0. 03, 0.06, 0.1 mg kg(-1)day(-1)) or distilled water for 16 days after the immunization. FTY720 suppressed the incidence and intensity of EAU in a dose-dependent manner as demonstrated by clinical and histological examinations. The drug significantly suppressed the serum levels of antibodies to S-antigen and antigens-specific lymphocyte proliferation. The number of peripheral lymphocytes, but not neutrophils, was markedly reduced by FTY720 treatment. FTY720 also suppressed the intensity of EAU when it was given from the day of EAU onset. These results indicate that FTY720 has intense immunosuppressive effects on EAU in rats and may be a potential candidate for use in the treatment of patients with autoimmune uveitis.
Kurose
S
S
Department of Ophthalmology, Kurume University School of Medicine, Fukuoka, Japan.
Ikeda
E
E
Tokiwa
M
M
Hikita
N
N
Mochizuki
M
M
D000818:Animals; D000906:Antibodies / Q000097:blood; D019393:Arrestin; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D016009:Chi-Square Distribution; D004305:Dose-Response Relationship, Drug; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D011409:Propylene Glycols / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000188:drug therapy* / Q000276:immunology; D013110:Sphingosine / Q000031:analogs & derivatives; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology
D000906:Antibodies; D019393:Arrestin; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine