Effects of mycophenolate mofetil in the development of systemic lupus erythematosus in (NZBxNZW)F1 mice

Abstract

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) is a chronic and progressive autoimmune syndrome characterized by the production of multiple autoantibodies (autoAb) resulting in the generation of circulating immune complexes (IC). The deposition of these IC leads to the development of tissue lesions such as glomerulonephritis. The study of several strains of mice that spontaneously develop an autoimmune syndrome resembling human SLE have been of considerable value to analyze cellular and molecular mechanisms responsible for the development of the disease as well as to explore the efficiency of different therapies using immunesuppressive drugs. One of these new immunosuppressive agents, Mycophenolate Mofetil (MMF), have been used successfully to prevent SLE in several lupus-prone mice such as MRL.1pr and (NZBxNZW)F1 mice. However, the precise mechanism by which MMF modulates the development of SLE in these animals remains controversial. Whereas in some studies the therapeutic effect of MMF is secondary to the inhibition of autoAb production, in others the administration of MMF blocks the development of IC-mediated glomerulonephritis but not the production of autoAb. To gain insight into the mechanisms responsible for the therapeutic effect of MMF, in the present study (NZBxNZW)F1 female mice have been treated with either high or low doses of MMF from 3 months of age, when increased serum levels of anti-nuclear autoAbs are already present. MATERIAL AND METHODS