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Fast, E.* ; Jakobs, J.* ; Bertram, J.* ; Wessels, I. ; Sailer, J.* ; Michalke, B.* ; Rink, L.*

Zinc, Fe2+ and Fe3+ differentially influence IFN-γ production in human peripheral blood mononuclear cells.

J. Nutr. Biochem., DOI: 10.1016/j.jnutbio.2025.110194:110194 (2025)
Postprint Research data DOI PMC
Open Access Green
BACKGROUND: Iron overload is a common phenomenon in patients undergoing transfusions or organ transplantation. Clinical studies indicate that iron overload interferes with immune function. Baseless supplementation of iron leads to higher morbidity and mortality. In iron overload T-cell differentiation is skewed towards a Th2 response, with lower levels of interferon (IFN)-γ. Zinc is known for its immune balancing abilities, e.g. by induction of regulatory T cells. This study aims to investigate the interaction of iron and zinc in mixed lymphocyte cultures (MLC). METHODS: MLC, peripheral blood mononuclear cells (PBMC) stimulation with phytohemagglutinin, ELISA, PCR, ICP-MS RESULTS: Zn2+ supplementation leads to a significantly lower IFN-γ production in MLC compared with control (p<0.03). Fe2+ supplementation lowers the IFN-γ production in MLC (P<0.0017), too. However, Fe3+ has a slightly increasing effect on IFN-γ release which differs significantly from Fe2+ (p<0.03). In 2,2-Bipyridyl-induced iron deficiency IFN-γ production is lowered (p<0.0003), whereas zinc deficiency does not significantly affect IFN-γ production. Examinations of Interleukin (IL)-2 and IL-6 show comparable tendencies. The Fe2+ effect can be imitated by sodium sulfite. Fe3+ treatment increases intracellular free iron in PBMC significantly compared to Fe2+ treatment (p<0.02). CONCLUSION: Iron (II) and zinc both suppress cytokine production in MLC. Fe3+ shows a significantly different effect on IFN-γ production. The underlying mechanism is likely a donation of electrons by Fe2+ or oxidative stress. These findings provide mechanistic insights on how the oxidation state of iron differentially modulates human immune cell function and highlights the importance of iron speciation in nutritional immunology.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cytokine Production ; Immunology ; Iron ; Mixed Lymphocyte Culture ; Zinc
ISSN (print) / ISBN 0955-2863
e-ISSN 0955-2863
Journal Journal of Nutritional Biochemistry, The
Quellenangaben Volume: , Issue: , Pages: , Article Number: 110194 Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Institute for Allergy Research (IAF)