Long term administration of cyclophosphamide in MRL/1 mice. I. The effects on the development of immunological abnormalities and lupus nephritis.

Weekly injection of cyclophosphamide (Cy) into MRL/Mp-lpr/lpr (MRL/l) mice, at a dose of 10-20 mg/kg, from 1 month of age prevented the development of generalized lymph node enlargement, decreased serum levels of anti-DNA antibodies and immune complexes, and markedly prolonged their life span. Cy effectively suppressed enhanced differentiation of B cells, as evidenced by decreased number of immunoglobulin secreting cells in the spleen. Cy was also shown to suppress abnormal expansion of Thy-1 positive cells in lymphoid organs of MRL/1 mice. These results suggested that Cy prevented the development of murine lupus like syndrome in MRL/1 mice through suppression of spontaneous polyclonal B cell activation and also by reducing the number of T cells to exert excessive helper activity on B cells.