The following differential effects of immunosuppressive therapy with Cyclophosphamide (CYCLOPH) and 6-mercaptopurine (6-MP) in the female NZB-NZW F1 hybrid strain have been observed: (1) CYCLOPH but not 6-MP significantly decreased antinuclear antibody level. (2) Both CYCLOPH and 6-MP significantly decreased glomerular cell proliferation. (3) Both CYCLOPH and 6-MP significantly arrested progression of glomerulosclerosis. (4) While CYCLOPH significantly diminished Ig deposition in the glomeruli, 6-MP had no effect on this phenomenon. (5) While CYCLOPH decreased subepidermal globulin deposition in the skin, 6-MP appeared actually to enhance subepidermal staining. Thus, the present studies demonstrated that CYCLOPH was superior to 6-MP in four of the five parameters studied. In the case of one parameter, Ig staining of the skin, 6-MP actually produced enhancement of the staining. Both CYCLOPH and azathioprine which is a derivative of 6-MP, are currently being used for the treatment of human SLE. The present findings suggest that of the two, CYCLOPH may be the drug of choice.
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