There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Zinc is known to be essential for all highly proliferating cells in the human body,
especially the immune system. A variety of in vivo and in vitro effects of zinc on
immune cells mainly depend on the zinc concentration. All kinds of immune cells show
decreased function after zinc depletion. In monocytes, all functions are impaired,
whereas in natural killer cells, cytotoxicity is decreased, and in neutrophil granulocytes,
phagocytosis is reduced. The normal functions of T cells are impaired, but autoreactivity
and alloreactivity are increased. B cells undergo apoptosis. Impaired immune functions
due to zinc deficiency are shown to be reversed by an adequate zinc supplementation,
which must be adapted to the actual requirements of the patient. High dosages of zinc
evoke negative effects on immune cells and show alterations that are similar to those
observed with zinc deficiency. Furthermore, when peripheral blood mononuclear cells
are incubated with zinc in vitro, the release of cytokines such as interleukins (IL)-1
and -6, tumor necrosis factor-alpha, soluble IL-2R and interferon-gamma is induced.
In a concentration of 100 micro mol/L, zinc suppresses natural killer cell killing
and T-cell functions whereas monocytes are activated directly, and in a concentration
of 500 micro mol/L, zinc evokes a direct chemotactic activation of neutrophil granulocytes.
All of these effects are discussed in this short overview.
Zinc is known to play a central role in the immune system, and zinc-deficient persons experience increased susceptibility to a variety of pathogens. The immunologic mechanisms whereby zinc modulates increased susceptibility to infection have been studied for several decades. It is clear that zinc affects multiple aspects of the immune system, from the barrier of the skin to gene regulation within lymphocytes. Zinc is crucial for normal development and function of cells mediating nonspecific immunity such as neutrophils and natural killer cells. Zinc deficiency also affects development of acquired immunity by preventing both the outgrowth and certain functions of T lymphocytes such as activation, Th1 cytokine production, and B lymphocyte help. Likewise, B lymphocyte development and antibody production, particularly immunoglobulin G, is compromised. The macrophage, a pivotal cell in many immunologic functions, is adversely affected by zinc deficiency, which can dysregulate intracellular killing, cytokine production, and phagocytosis. The effects of zinc on these key immunologic mediators is rooted in the myriad roles for zinc in basic cellular functions such as DNA replication, RNA transcription, cell division, and cell activation. Apoptosis is potentiated by zinc deficiency. Zinc also functions as an antioxidant and can stabilize membranes. This review explores these aspects of zinc biology of the immune system and attempts to provide a biological basis for the altered host resistance to infections observed during zinc deficiency and supplementation.
Intracellular zinc is thought to be available in a cytosolic pool of free or loosely bound Zn(II) ions in the micromolar to picomolar range. To test this, we determined the mechanism of zinc sensors that control metal uptake or export in Escherichia coli and calibrated their response against the thermodynamically defined free zinc concentration. Whereas the cellular zinc quota is millimolar, free Zn(II) concentrations that trigger transcription of zinc uptake or efflux machinery are femtomolar, or six orders of magnitude less than one atom per cell. This is not consistent with a cytosolic pool of free Zn(II) and suggests an extraordinary intracellular zinc-binding capacity. Thus, cells exert tight control over cytosolic metal concentrations, even for relatively low-toxicity metals such as zinc.
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.