MYCOPHENOLATE MOFETIL LIMITS RENAL DAMAGE AND PROLONGS LIFE IN MURINELUPUS AUTOIMMUNE-DISEASE

Classical immunosuppressants like cyclophosphamide give excellent resu lts in human lupus nephritis. However, they augment malignancies and v iral infections. Here we investigated the effect of the new immunosupp ressant agent, mycophenolate mofetil (MMF), in New Zealand Black x New Zealand White (NZBxW) F1 hybrid mice, a model of genetically determin ed immune complex disease that mimics systemic lupus in humans. MMF ha s a selective antiproliferative effect on T- and B-lymphocytes, inhibi ts antibody formation and blocks the glycosylation of lymphocyte glyco proteins involved in the adhesion of leukocytes to endothelial cells. Two groups of NZBxW mice were used: group 1 (N = 20) given daily MMF ( 60 mg/kg p.o.) and group 2 (N = 15) given daily vehicle alone. Treatme nt started at three months of age and lasted until the death of the an imals. Results showed that percentage of proteinuric mice was signific antly reduced by MMF treatment and serum BUN levels were also lower th an vehicle. MMF had a suppressive effect on autoantibody production an d protected animals from leukopenia and anemia. Life survival of MMF t reated lupus mice was significantly improved in respect to untreated a nimals. Thus, MMF delayed renal function deterioration and prolonged l ife survival in murine lupus nephritis. MMF has been already recognize d as reasonably well tolerated in renal transplant patients and despit e its gastrointestinal toxicity its overall safety profile appears sup erior to azathioprine. Human studies are needed to establish whether M MF may function as a steroid-sparing drug in lupus nephritis.