Comparison of therapeutic and immunosuppressive effects of azathioprine, prednisolone and combined therapy in NZP-NZW mice.

Abstract

AbstractSince NZB/NZW mice develop an immune nephritis similar to that of systemic lupus erythematosus in man, a study was designed in these mice to compare the clinical and immunologic effects of three immunosuppressive drug regimens. For 72 weeks, groups of 20 mice received daily oral therapy with a) no drugs, b) azathioprine, c) prednisolone or d) combined azathioprine‐prednisolone. The combined regimen was superior to either drug used alone in preventing deaths from renal disease. Prednisolone alone also prolonged life significantly, but not as effectively as combination therapy. Azathioprine alone was not effective. All drugs suppressed the antibody response to an exogenous antigen (Vi polysaccharide) equally well. None of the drug regimens prevented the appearance of proteinuria, antinuclear antibodies, Coombs' antibody, or γ‐globulin deposits in glomeruli. However, the ability of a therapeutic regimen to suppress antibodies to native DNA correlated well with its ability to suppress renal disease. No malignancies were found among 73 animals autopsied, but significant hepatic damage occurred in the groups receiving prednisolone. Thus, combined therapy was superior to either drug used alone, and the immunosuppressive effect of greatest clinical importance seemed to be the ability to prevent formation of anti‐DNA antibodies.