Nutritional factors and autoimmunity. I. Immunopathology of zinc deprivation in New Zealand mice

Although alteration of dietary protein and lipid content has been demonstrated to modify the progression of murine autoimmune disease, relatively little is known regarding the influence of trace metal nutriture on such immunologic phenomena. To investigate such interactions, groups of NZB mice at 6 wk and 6 mo of age were fed diets containing 100 ppm zinc (control), 9 ppm zinc (designated marginal deficiency), 5 ppm zinc (designated moderate deficiency), and 2.5 ppm zinc (designated severe deficiency). Further, to control for the inanition of mice fed the zinc deficient diets, a group of mice were pair-fed the control diet in amounts equal to the intake of mice fed 5 ppm zinc. NZB mice who began the study at 6 wk of age and who were fed 9 ppm zinc experienced a progression of autoimmune disease similar to that observed in the ad libitum-fed control mice. In contrast, young mice fed either 5 or 2.5 ppm zinc showed a delay in the onset of autoimmune hemolytic anemia, as reflected by significantly higher packed cell volume and hemoglobin values, lower titers of anti-erythrocyte autoantibodies and serum immunoglobulins, and prolonged lifespan. The delay in the progression of these features was partially accounted for by depression of food intake and consequent caloric deprivation. However, mice fed 5 ppm zinc had higher packed cell volume and hemoglobin values, and lower anti-erythrocyte autoantibody titers and serum immunoglobulin levels than did their pair-fed controls, indicating that deprivation of zinc accounted for a significant share of the alteration in autoimmunity by nutritional manipulation. In contrast, NZB mice that began to consume the diets at 6 mo of age showed a moderate slowing but not a reversal of the autoimmune hemolytic anemia. The retardation of autoimmunity in older NZB mice was almost entirely due to the inanition that accompanied zinc deprivation, as reflected by a similar slowing of the onset of autoimmune hemolytic anemia in pair-fed controls. These results reaffirm the possibility of utilizing nutritional factors to alter murine autoimmune disease, and further establish the potential importance of trace metals in the development and maintenance of immunocompetence.