Studies of Nutrition and Autoimmunity. Failure of Zinc Deprivation to Alter Autoantibody Production when Initiated in Disease-Established Mice

Abstract

Earlier studies have demonstrated that zinc deprivation, when begun in young NZB mice, can retard the development of autoimmunity and result in an increased life span. The present study evaluated the possible benefits of zinc deprivation in NZB mice with established disease, as this model is more relevant to the human patient. Female NZB mice aged 6–8 mo were fed diets containing either 80 μg Zn/g and 10 μg Cu/g (control) or 1 μg Zn/g and 10 μg Cu/g (zinc-deficient) for 4 mo. In addition, another group was fed a diet containing 1 μg Zn/g and 100 μg Cu/g to determine whether zinc deficiency could be exacerbated by high dietary copper through a competition of copper with zinc at the intestinal level (zinc deficient + high copper). A fourth group of mice was fed the control diet at the same intake as that of the zinc-deficient group in order to control for the inanition associated with zinc deficiency (restricted intake). Regardless of dietary treatment, all mice developed antierythrocyte antibodies at the same rate. At the end of 4 mo, 82% of the control and the restricted-intake groups had survived, whereas the zinc-deficient group had a 38% survival rate and the zinc-deficient + high copper group had a 50% survival rate. These observations show that, in contrast to findings with younger NZB mice, zinc deprivation of adult NZB mice with established autoimmunity will not improve survival. Indeed, severe zinc deficiency increased the mortality rate, demonstrating the need to consider the potential hazards of dietary extremes.