Stimulated autoantibody response and increased longevity in NZB/NZW mice treated with cyclophosphamide and tilorone

Abstract

The experiment described in this report was designed to study the effects of immunostimulatory therapy in cyclophosphamide-treated hybrid New Zealand mice. Autoantibodies, renal histology and neoplasms were studied in seventeen female NZB/NZW mice treated with daily injections of the potent immunosuppressive drug, cyclophosphamide. Results were compared with fifteen female NZB/NZW mice who received both cyclophosphamide and tilorone, an interferon inducer which stimulates the immune system. Fifteen control mice received saline. The controls died with spontaneous arteritis and immune complex glomerulonephritis; their mean age at death was 46 weeks. In the cyclophosphamide group anti-DNA antibodies and renal disease were suppressed. Mean longevity was prolonged significantly to 80 weeks. Two mice died of iatrogenic causes, and the remaining fifteen mice died with neoplasms. Eleven mice had multiple neoplasms; a total of twenty-seven neoplasms appeared. In mice receiving combination therapy, autoantibody responses were not suppressed. Nevertheless, glomerulonephritis was controlled partially and the mean lifespan was prolonged to 82 weeks. Eighteen neoplasms appeared in ten mice in the combination treatment group, and five mice had more than one neoplasm. The appearance of lymphomas was delayed in mice receiving two drugs. It was concluded that concurrent therapy with tilorone stimulated autoantibody production and altered the expected pattern of neoplasia in cyclophosphamide-treated NZB/NZW mice.