The effect of copper deficiency on the immune response in mice.

Weanling female Swiss mice were fed copper-deficient or copper-replete diets for 28 days. Mice fed the copper-deficient diet exhibited typical signs copper deficiency, which included reduced weight gains, anemia, and low liver copper concentrations. The effect of copper deficiency on antibody production, in particular, T-lymphocyte dependent and independent antibody responses, lymphocyte blastogenesis, and sensitivity to endotoxin were evaluated. Antibody production against sheep red blood cells, a T-lymphocyte dependent response, was suppressed in copper-deficient mice (P less than .0001). In contrast, antibody production against dinitrophenyl-ficoll, a T-lymphocyte independent response was not altered by copper deficiency (P = 0.90). Lymphocyte blastogenesis studies demonstrated that copper deficiency did not alter T-lymphocyte blastogenesis induced by concanavalin A (P = 0.27) or B-lymphocyte blastogenesis induced by Escherichia coli lipopolysaccharide (P = 0.40). These results indicate that the immunosuppressive effects are not due to an impairment of lymphocyte blastogenesis, an intermediate step involved in the generation of an immune response, but rather are a manifestation of impaired T-lymphocyte function associated with antibody production. Increased susceptibility to endotoxin, involving nonspecific defense mechanisms, was also observed in copper-deficient mice. Mortality associated with the endotoxin was 68% in the copper-deficient mice as compared to 35% in the copper-replete mice (P = 0.0026). Impaired T-lymphocyte dependent antibody production and enhanced susceptibility to endotoxin were observed in copper-deficient mice exhibiting classical manifestations of copper deficiency.