|Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Objective : Hydroxy-Methylglutaryl Coenzyme A(HMG-CoA) reductase inhibitors (statins) possesses anti-inflammatory and immunomodulatory effects. Its efficacy was demonstrated by in vivo model of collagen induced arthritis(CIA), and experimental allergic encephalitis(EAE) model mouse. To elucidate beneficial effects of statins on another autoimmune diseases, we conducted an in vivo treatment of MRL-lpr/lpr mouse, Fas deficient human Systemic lupus Erythematosus(SLE) model mouse by Fluvastatin.
Methods : female MRL-lpr/lpr mice age between 4-5weeks were devided into 3 groups(n=20/group) : On 16 weeks, each group was administered intraperitonially with saline(control, C), Fluvastatin 10mg/kg(F), or methylprednisolone 10mg/kg(P) 3 times a week. Effects were evaluated by urine proteins, urine occult blood, anti-double strand antibody, serum creatinine, creatine phosphokinase, total cholesterol level, IFN-gamma, and survival rate.
Result s: Eight weeks after treetment, Urinary proteins(C=1.17,F=0.47), urine occult blood(C=1.44,F=0.58), serum cholesterol level(C=234.8,F=179.8), and interferon gamma (C=41.3ng/ml, F=18.7ng/ml). were decreased in Fluvastatin treated group than in control group. Elevation of creatine phosphokinase was not observed. Four months after treatment, although it was not statistically significant, there was a tendency that Fluvastatin treated group showed a better survival rate than control group.
Conclusion : There is a possibility that fluvastatin shifts Th1/Th2 balance towards Th2 by decreasing IFN-gamma, thereby improves their urinary findings, and even their survival rate.