Selective suppression of autoantibody responses in NZB/NZW mice treated with long-term cyclophosphamide

Autoimmune responses were assayed in 80 cyclophosphamide-treated and control NZB/NZW mice over a period of 1 year. Fluctuation between positive and negative immunofluorescent heterogeneous ANA tests and daily alterations of ANA titers were detected in young mice of both sexes. Although high-dose cyclophosphamide therapy (8 mg/kg/day) failed to prevent the spontaneous appearance of ANA, titered ANA values were partially suppressed in high-dose treated mice. This study permitted sequential comparisons between ANA titers and anti-DNA as useful indices of cyclophosphamide-induced suppression of autoimmune disease. ANA titers were relatively resistant to cyclophosphamide therapy. Antibodies directed specifically against DNA were suppressed mice receiving high-dose cyclophosphamide. In treated animals, decreased anti-DNA levels were associated with protection from severe glomerulonephritis and renal vasculitis. Treatment with low-dose cyclophosphamide (1 mg/kg/day) appeared paradoxically to stimulate autoantibody production and renal disease/vasculitis.