Development of autoimmunity in MRL/lpr mice and the effects of drugs on this murine disease

Abstract

MRL/lpr mice spontaneously develop a systemic Lupus erythematosus (SLE)-like disease with a wide range of clinical and serological characteristics that mimic not only human SLE but other autoimmune disorders. such as Sjögren's syndrome, and rheumatoid arthritis (RA). Unlike other murine SLE-like disorders, these mice have circulating rheumatoid factor (RF) and develop histological changes in their joints. Therapy of this disease with cyclophosphamide (CY), cyclosporin A, prednisolone, or leflunomide (HWA 486) resulted in very differing effects. Treating these mice with HWA 486 or cyclophosphamide (CY) resulted in a decrease in the amount of autoantibodies, and immune complex deposits on the glomeruli. HWA 486 therapy led to restoration of the depressed immune response of MRL/lpr mice. In the established disease, prednisolone (Pr), cyclosporin A (CSA), and HWA 486 could inhibit the proteinuria and return the urine-protein values to normal levels, but, unlike HWA 486, neither PR nor CSA could extend the longevity of these animals. The MRL/lpr mouse should prove to be very useful as a model for SLE, RA, and for discovering novel drugs to combat such disorders.