| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Objectiv.
We have shown that treatment of MRL-lpr/lpr mice whh FTY720, a novel immunosuppressant, ameliorates glomerulonephritis and prolongs the liie-span of this strain. In this study, we evaluated the effects of FTY720, on an additional experimental murine model of systemic lupus erythematosus (SLE) ; the female NZBxNZWF1 (B/W F1).
Methods.
Since 8 months of age, 12 female B/W F1 mice received oral 2 mg/kg each of FTY720, methylprednisolone (mPSL) or vehicle, three times in week. Therapeutic efficacy was evaluated by levels of anti-dsDNA antibodies in serum and the survival rate. In parallel, phenotypes of splenocytes, peritoneal exudates cells and bone marrow cells, as well as immunohistochemistry of the kidney, were examined.
Results.
FTY720 significantly reduced the number of CD5^+ B cells from the peritoneal cavity, suppressed the production of anti-dsDNA antibodies (FTY720 vs control : 213±88U/ml vs 509±196U/ml at 11 months of age, p<0.05) and decreased the deposition of IgG in glomeruli from compared to control animals. At 13 months of age, the survival rate in the FTY720-treated mice was 75.0% compared to 25.0% in controls (p<0.01). Administration of FTY720 produced no adverse effects, such as liver dysfunction, or hyperglycemia seen in the mPSL-treated mice.
Conclusion.
FTY720 suppressed the development of autoimmunity and prolonged die lifespan of female B/W F1 mice. Suppression of autoimmunity was achieved without obvious side effects. Hence, it could be useful for primaiy or adjunctive therapy of human SLE.
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