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 Th(0) human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB 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-1beta, and IL-8 cytokines and mRNA. In these cells, zinc induced A20, a zinc finger protein that inhibited NF-kappaB 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 antioxidant agent.
Prasad
Ananda S
AS
Department of Internal Medicine, Division of Hematology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. prasada@karmanos.org
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics; D019587:Dietary Supplements; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D007376:Interleukin-2 / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D015032:Zinc / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use
D000975:Antioxidants; D016207:Cytokines; D007376:Interleukin-2; D016328:NF-kappa B; D012333:RNA, Messenger; D015032:Zinc