Chronic Intake of a Marginally Low Copper Diet Impairs In Vitro Activities of Lymphocytes and Neutrophils from Male Rats despite Minimal Impact on Conventional Indicators of Copper Status

We investigated the impact of chronic intake of a diet marginally low in Cu on traditional indicators of Cu status and in vitro activities of splenic mononuclear cells and neutrophils. Pregnant Sprague-Dawley rats were fed diets containing either 2.8 (LCu) or 6.7 [adequate (ACu)]mg Cu/kg from midgestation through lactation. Weaned male and female offspring were fed the same diets as their dams until 6 months of age. Dietary Cu level did not alter growth, heart weight, the concentrations of Cu or the activities of cuproenzymes in serum and most tissues. In contrast, splenic mononuclear cells (MNC) from males, but not females, fed the LCu diet were less responsive to in vitro mitogenic activation and generated less interleukin-2 bioactivity than cultures prepared from males fed the ACu diet. Repletion with the ACu diet for 2 wk restored in vitro activities of splenic MNC to control levels. The phorbol myristate acetate-induced generation of superoxide anion by elicited neutrophils from male rodents fed the LCu diet was only 60% that of cells from the ACu diet group. Brain Cu in adult rats fed LCu diet was irreversibly decreased compared with those fed ACu diet. These data show that the in vitro activities of T lymphocytes and neutrophils isolated from adult male rats chronically fed a diet marginally low in Cu were significantly suppressed without marked alterations in the traditional indicators of Cu status.