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

Nutrition. 2007 Feb;23(2):157-63. doi: 10.1016/j.nut.2006.10.007. Epub 2006 Dec 5.

Abstract

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 microM) or 1 microM of N, N, N', N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) (a zinc-specific chelator). Phytohemagglutinin-induced cytokine release was measured by enzyme-linked immunosorbent 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 Th2/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Chelating Agents
  • Cytokines / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / metabolism
  • Middle Aged
  • Th1 Cells / drug effects*
  • Th1 Cells / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / metabolism
  • Trace Elements / immunology*
  • Trace Elements / metabolism
  • Trace Elements / pharmacology
  • Up-Regulation
  • Zinc* / immunology
  • Zinc* / metabolism
  • Zinc* / pharmacology

Substances

  • Chelating Agents
  • Cytokines
  • Trace Elements
  • Interleukin-10
  • Interferon-gamma
  • Zinc