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.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000917:Antibody Formation / Q000187:drug effects; D001327:Autoimmune Diseases / Q000188:drug therapy; D002250:Carbon Radioisotopes; D003201:Computers; D003520:Cyclophosphamide / Q000494:pharmacology* / Q000627:therapeutic use; D004247:DNA / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D007668:Kidney / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D008954:Models, Biological; D012737:Sex Factors
D000974:Antibodies, Antinuclear; D002250:Carbon Radioisotopes; D003520:Cyclophosphamide; D004247:DNA