Zinc and Regulation of Inflammatory Cytokines: Implications for Cardiometabolic Disease

Abstract

In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1β, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination.

Differential impact of zinc deficiency on phagocytosis, oxidative burst, and production of pro-inflammatory cytokines by human monocytes

“…5 One major monocyte function is cytokine production, and zinc influences the release of inflammatory cytokines, even though the results so far have been highly contradictory. 6 Lipopolysaccharide (LPS), part of the cell wall of gramnegative bacteria, is one of a myriad of agents that leads to secretion of monokines such as tumor necrosis factor (TNF)-a and interleukin (IL)-6. Their release in response to stimulation using LPS can be enhanced in peripheral mononuclear blood cells (PBMC) by zinc supplementation, 4,7 and intracellular zinc signals are required for the production of pro-inflammatory cytokines in response to LPS.…”

Zinc in Infection and Inflammation

“…In vitro studies using different cell types and zinc concentrations as well as the impact of chelating agents have made it obvious that the influence of zinc cannot be interpreted using a unilateral approach [35]. For instance, a study by Haase et al have revealed that zinc is necessary for the activation of lipopolysaccharide (LPS)-induced NF-κB signalling pathway, whereas chelating zinc with membrane permeable zinc specific chelator TPEN (N,N,N',N'-tetrakis-(2-pyridyl-methyl) ethylenediamine) completely blocked this pathway [36].On the other hand, there is a growing body of literature that supports the role of zinc as a negative regulator of NF-κB signalling pathways.…”

An immune response and an alveolar macrophage phenotype in asthma, gastroesophageal reflux disease and their concurrence

“…Важную роль в развитии данного воспалительного компонента, вероят-но, играет ядерный фактор транскрипции -NF-κB. Этот фактор вовлечен в процессы синтеза провоспалительных цитокинов и его активация, действительно, происходит в легких при повреждении, инфекциях, БА и других заболе-ваниях [20][21][22]. Поэтому NF-κB заслуживает внимания в качестве терапевтической мишени при лечении легочных осложнений ГЭРБ, БА и сочетанной патологии.…”

“…1, строка 12). Чтобы понять причину этих от-личий, надо учитывать, что основным источником IL-2 являются клетки Th1 [22]. В легких и БАЛЖ эти клетки есть, а в среде культивирования макрофагов -нет.…”