On the safety of treatment with bovine superoxide dismutase: production of a humoral antibody response in rabbits with repeated treatment.

Treatment of rabbits with sterile solutions of bovine Cu-Zn superoxide dismutase according to schedules recommended for radiation cystitis and radiation side effects has elicited the production of antibodies to the enzyme, detected in rabbit sera by a sensitive and specific radioimmunoassay. No antibodies were detected after a single treatment. However, on repeated administration of the enzyme all animals, including those that received 4 Gy whole body radiation prior to treatment, produced detectable antibody. Titers of antibody in sera rose progressively with repeated injections of the enzyme. Irradiation served merely to delay the onset of the immune response. In addition, human and bovine Cu-Zn superoxide dismutase have been found to be antigenically distinct when examined by competitive inhibition radioimmunoassay. These antigenic differences and the immunogenicity of the bovine enzyme in rabbits raise reasonable doubt as to the safety of administration of bovine superoxide dismutase to human patients. It is recommended that such patients be monitored for antibody production, preferably by radioimmunoassay.