title: T-helper type 1 cytokine release is enhanced by in vitro zinc supplementation due to increased natural killer cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Immunology, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Claudia H D
authors.initials: CH
authors.lastname: Metz
authors.forename: Anja K
authors.initials: AK
authors.lastname: Schröder
authors.forename: Silke
authors.initials: S
authors.lastname: Overbeck
authors.forename: Laura
authors.initials: L
authors.lastname: Kahmann
authors.forename: Birgit
authors.initials: B
authors.lastname: Plümäkers
authors.forename: Lothar
authors.initials: L
authors.lastname: Rink
mesh_terms: D000293:Adolescent; D000328:Adult; D002614:Chelating Agents; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D014131:Trace Elements / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation; D015032:Zinc / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D016207:Cytokines; D014131:Trace Elements; D016753:Interleukin-10; D007371:Interferon-gamma; D015032:Zinc