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.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000921:Antibody-Producing Cells / Q000187:drug effects; D000936:Antigen-Antibody Complex / Q000032:analysis; D001327:Autoimmune Diseases / Q000517:prevention & control*; D001402:B-Lymphocytes / Q000276:immunology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004277:DNA, Single-Stranded / Q000276:immunology; D005921:Glomerulonephritis / Q000517:prevention & control*; D008180:Lupus Erythematosus, Systemic / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000187:drug effects; D008221:Lymphoid Tissue / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011507:Proteinuria / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D004277:DNA, Single-Stranded; D003520:Cyclophosphamide