Zinc: Mechanisms of host defense

Zinc deficiency in humans decreases the activity of serum thymulin (a thymic hormone), which is required for maturation of T-helper cells. T-helper 1 (Th-1) cytokines are decreased but T-helper 2 (Th-2) cytokines are not affected by zinc deficiency in humans. This shift of Th-1 to Th-2 function results in cell-mediated immune dysfunction. Because IL-2 production (Th-1 cytokine) is decreased, this leads to decreased activities of natural-killer cell and T cytolytic cells, which are involved in killing viruses, bacteria, and tumor cells. In humans, zinc deficiency may decrease the generation of new CD4+ T cells from the thymus. In cell culture studies (HUT-78, a The human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappa B NF-kappa B) activation, phosphorylation of I kappa B, and binding of NF-kappa B to DNA are decreased and this results in decreased Th-1 cytokine production. In another study, zinc supplementation to humans decreased the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers. In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-1 beta, and IL-8 cytokines and mRNA. In these cells, zinc induced A20, a zinc finger protein that inhibited NF-kappa B activation via tumor necrosis factor receptor associated factor pathway, and this decreased gene expression of pro-inflammatory cytokines and oxidative stress markers. We conclude that zinc has an important role in cell-mediated immune functions and also functions as antiinflammatory and antioxicant agent.