T-helper type 1 cytokine release is enhanced by in vitro zinc supplementation due to increased natural killer cells

Objective: We examined the influence of zinc on T-helper type 1 (Th1)/T-helper type 2 (Th2) balance in human lymphocytes. Methods: Human peripheral blood mononuclear cells or diluted. whole blood were cultured for 8 d in the presence of zinc (30 or 60 mu M) or 1 mu M of N, N, N', N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) (a zinc-specific chelator). Phytohemagglutinin-induced cytokine release was measured by enzyme-linked immunosorbeni assay, and expression of CD56/CD69, CCR4/CD3, and CCR5/CD3 and intracellular labile zinc were detected by flow cytometry. Results: We found that our in vitro supplementation resulted in an increase of intracellular labile zinc comparable to that of a 7-wk administration of 10 mg of zinc per day in vivo. Zinc triggered interferon-gamma release and impaired interleukin-10 release. Phenotypically, a T`h2/Th1 shift could not be confirmed after detecting the Th1-specific chemokine receptor CCR5 or CCR4 for Th2 cells. Surprisingly, we detected a larger amount of CD56(+) cells after zinc stimulation, leading us to the conclusion that the amount of interferon-gamma release after zinc supplementation might be attributed to the upregulation of natural killer cells after in vitro zinc supplementation rather than to a Th2/Th1 shift. Conclusion: We suggest that a nutritional intake of 10 mg of zinc increases the quantity of interferon--gamma-producing natural killer cells and strengthens the immune system against neoplasms and viral infections. (C) 2007 Elsevier Inc. All rights reserved.