Seminar by Prof. Lothar Rink

Uniklinik RWTH Aachen (Germany)

Zinc homeostasis and the immune system

Zinc is an essential trace element for the immune system and zinc deficiency compromises the function of all cells of the immune system. However, an excess of zinc have negative effects on the immune system too. Therefore zinc homeostasis must be delicately regulated for an effective immune response.
Zinc deficiency is accompanied by signs of chronic inflammation. The overexpression of proinflammatory cytokines is due to epigenetic changes in the promoter regions of proinflammatory cytokines during zinc deficiency. Whereas zinc deficiency alters the promoter regions into a more accessible form, a supplementation with zinc reconstructed the promoter to a closed form. However, this is not a complete suppression of proinflammatory cytokines, but a regulation of the threshold of gene activation. This resulted in a higher activity of monocytes under zinc deficient conditions.
For T cell immunity the regulation by zinc is the other way around. Zinc supplementation induces a shift towards TH1 immune reactions, which is controlled by regulatory T cells. The production of interferon-g and interleukin-2 increases with zinc supplementation. However, the induction of regulatory T cells limits this effect and is dependent on the zinc concentration and the stimuli used. A regulation of immune responses in dependence of the zinc concentration could be shown in different models like transplantation, allergy and ageing.
Taken together, the immune response is directly regulated by the zinc level and could be manipulated by zinc supplementation in vivo. Therefore, depending on the dose, zinc could be used as immunostimulant as well as immunosuppressant.