Cadmium-Induced Immunopathology Is Prevented by Zinc Administration in Mice

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Abstract
Six-week-old C57BL/6 male mice were exposed to 50 mg cadmium/L drinking water (50 ppm) for 3 wk, and killed at 0, 3 and 6 wk after cessation of treatment. In some groups, 500 mg zinc/L was added to the drinking water (500 ppm) with or after cadmium treatment. The number of direct and indirect splenic plaque-forming cells was higher in cadmium-treated mice at 0 wk than in untreated controls. Concurrent zinc administration prevented the enhancement of plaque-forming cell response. Proliferative response of spleen cell culture to the T-cell mitogens phytohemagglutinin and concanavalin A was slightly high in cadmium-treated mice at 0 wk and zinc administered after exposure to cadmium tended to lower it. The number of Lyt-2 positive cells in the spleen was lower and the ratio of L3T4 to Lyt-2 positive cells, reflecting the balance of immunoregulatory T-lymphocytes, was higher after cadmium treatment than in untreated controls. Concurrent zinc administration prevented the alteration of T-cell subsets. Cadmium and zinc treatment had no effect on liver, kidney, spleen and thymus weights and lymphocyte content of spleen, thymus and peripheral blood. Use of immunofluorescence with anti-mouse IgG and C3 showed no evidence of an autoimmune reaction in kidney sections. Liver and kidney cadmium concentrations were high at all observation times in the cadmium-treated animals. Tissue cadmium levels were lower in mice treated with both zinc and cadmium than in those treated with cadmium alone. The results suggest that a relatively low dose of cadmium exposure produces immune alterations that can be prevented by a moderately large dose of zinc.