Effects of mycophenolate mofetil and rapamycin on inflammatory and fibrotic mediators in NZB/W mice with active nephritis

Session: Glomerulonephritis - Experimental models: SA038INTRODUCTION AND AIMS: Rapamycin may have a role in the treatment of lupus nephritis due to its immunosuppressive and anti-proliferative properties. This study compared the effect of rapamycin and mycophenolate mofetil (MMF) on inflammatory and fibrotic mediators in a murine model of lupus nephritis. METHODS: Female NZB/W mice with established nephritis and proteinuria >3g/l were randomized to receive treatment with vehicle alone (control), MMF (100mg/kg/day), or rapamycin (3mg/kg/day) for 2, 6 and 12 weeks (n=6 for all time points in each group), and clinical parameters and renal histology assessed. RESULTS: Urine albumin-to-creatinine ratio and serum anti-DNA antibodies increased progressively in control mice. These abnormalities were ameliorated in both MMF and rapamycin treated groups (P<0.01 for both compared to control mice after 12 weeks). Both MMF and rapamycin treatment resulted in reduced glomerular expansion (glomerular tuft area: 4252.15±324.15, 2645.76±564.21 and 2648.21±468.32μm2 for control, MMF and rapamycin respectively, P