Impaired immunologic ontogeny in postnatal zinc deprivation.

The effects of zinc deprivation upon the normal immunologic ontogeny of outbred N:NIH(S) mice was investigated by feeding lactating dams, from the day of parturition, and their pups to 8 weeks of age, a diet containing EDTA-washed isolated soy protein and 9 ppm (marginal zinc deficiency), 5 ppm (moderate zinc deficiency) or 2.5 ppm (severe zinc deficiency) zinc. Two groups of controls were provided with the same diet, but containing 100 ppm zinc; one group was fed ad libitum, the other was pair-fed to the level of food intake observed in the moderately deprived animals (5 ppm zinc). Severe growth retardation of lymphoid tissues, most notably thymus, was observed in all mice deprived of zinc. Indeed, the magnitude of splenic and thymic hypogenesis was directly dependent upon the severity of the dietary zinc deficit. Furthermore, zinc-deprived pups exhibited a significantly decreased splenic cellularity whether assessed per spleen or as a function of spleen weight, including a sharp reduction in both red and white cell counts. Similarly, at 4 weeks of age direct splenic plaque-forming cell responses to sheep erythrocyte immunization were dramatically diminished in mice that were moderately and severely deprived of zinc during the postnatal period. Finally, a striking and indicative feature of the critical import of zinc in immune maturation was the observation that these zinc-deficient mice at 4 weeks of age exhibited a highly disordered serum immunoglobulin profile, with absence of detectable IgM, IgG2a and IgA along with greatly elevated serum levels of IgG1. We suggest that deficiency of zinc during growth and development may predispose in a major way to acquired immune deficiency and opportunistic infection.