Severe or Marginal Copper Deficiency Results in a Graded Reduction in Immune Status in Mice

Abstract

From birth mice received diets containing copper at 0.5, 1, 2 or 6 mg/kg diet. At 8 wk of age they were killed and copper status and immune responsiveness were determined. Only the groups that received copper at 0.5 or 1 mg/kg showed signs of copper deficiency, such as reduced serum ceruloplasmin, hemoglobin, hematocrit and red blood cell counts and characteristic changes in organ pathology. Body and lymphoid organ weights were altered in the groups that received copper at 0.5 or 1 mg/kg. Males were more severely affected than females. A dose-related reduction in splenic T-cell subpopulations was noted in the 0.5 and 1 mg/kg groups. Responses to lipopolysaccharide challenge were reduced, and an increase in spontaneous cycling cells was noted in the groups receiving copper at 0.5 or 1 mg/kg. Only the group receiving copper at 0.5 mg/kg had increased stem cell activity; this increase was probably due to increased erythropoiesis to meet increased demands for red blood cells in this group. These data indicate that only groups receiving copper at 0.5 or 1 mg/kg in the diet were depleted and marginally depleted in copper, respectively, and that immune hyporesponsiveness differs between the depleted and marginally depleted groups.

Is Low Copper Status Immunosuppressive?

“…It usually is assumed that the numbers of antigen-presenting cells and target lymphocytes are similar in cultures prepared from control and test tissues when evaluating cellular responses to mitogenic stimulation. Flow cytometric analysis of splenic and peripheral blood mononuclear cells from rats (Bala et al 1990, Bala et al 199 1) and murine splenocytes (Lukasewycz et al 1985, Mulhem andKoeller 1988) has shown that the relative percentage of T cells is decreased about 25% in severely copper-deficient animals, whereas the macrophage population is relatively resistant to the nutritional insult. The degree of suppression of 3H thymidine incorporation into DNA in splenic mononuclear cell cultures prepared from copper-deficient rats is much greater than can be attributed to the reduced number of T cells (Bala et al 1990, Bala et al 1991.…”

The immune system as a physiological indicator ofmarginal copper status?

“…Phenotypic profiles of lymphoid and myeloid cells from mice (Lukasewycz et al 1985;Mulhern & Koller, 1988), and mononuclear cells (MNC) from rat spleen (Bala et al 1991b) and peripheral blood (Bala et al 1990) are altered by Cu deficiency. More specifically, there is a general reduction in T lymphocytes, sometimes elevation of B lymphocytes but never a reduction, and in one study an increase in macrophages was seen (Bala et al 1991b).…”

“…In severe Cu deficiency, phenotypic profiles of lymphoid and myeloid cells from mice (Lucasewycz et al 1985;Mulhern & Koller, 1988) and MNC from rat spleen (Bala et al 1991b) and peripheral blood (Bala et al 1990) are altered. More specifically, in Cu-deficient mice (Lukasewycz et al 1985), there was a statistically significant increase in the number of surface immunoglobulinbearing cells, in terms of relative number of cells per spleen.…”

“…It has also been demonstrated (Bala & Failla, 1993) that feeding Cu-deficient rats a Cu-adequate diet increased the percentage of splenic CD4+ cells back to control levels, whereas relative percentage and total numbers of splenic CD8+ cells were unaffected by depletion and repletion. A study by Mulhern & Koller (1988) demonstrated that in marginal and severely Cu-deficient rats there was a dose-dependent reduction in Thy-1·2 (T cell marker) and Lyt-1 (CD4+).…”

Nutrition and Cytokine Action

“…Indirect evidence that Cu deficiency may reduce cytokine production comes from a study by Mulhern & Koller (1988), in which mice receiving Cu-deficient diets showed only 64% of the normal increase in spleen cells when exposed to E. coli lipopolysaccharide (LPS). There is a growing body of evidence that deficiencies of Cu and Zn limit the ability of animals to raise concentrations of proteins rich in these trace elements.…”