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 highdose cyclophosphamide therapy (8 mg/kg/day) failed to prevent the spontaneous appearance of ANA, titered ANA values were partially suppressed in highdose 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 relalively resistant to cyclophosphamide therapy. Antibodies directed specifically against DNA were suppressed in mice receiving high‐dose cyclophosphamide. In treated animals, decreased anti‐DNA levels were associated with protection from severe glomerulonephritis and renal vasculitis. Treatment with lowdose cyclophosphamide (1 mg/kg/day) appeared paradoxically to stimulate autoantibody production and renal disease/vasculitis.