Nutritional deficiency of zinc is widespread throughout the developing world. Zinc deficient subjects experience increased susceptibility to a variety of infections. Zinc deficiency in an experimental human model caused an imbalance between Th1 and Th2 functions. Production of IFN-β₯ and IL-2 (products of TH1) were decreased, whereas production of IL-4, IL-6 and IL-10 (products of Th2) were not affected due to zinc deficiency. Zinc deficiency decreased NK cell lytic activity and percentage of precursors of cytolytic T cells. In HUT-78, a Th0 cell line, zinc deficiency decreased gene expression of deoxythymidine kinase (TK), delayed cell cycle and decreased cell growth. Gene expression of IL-2 and IL-2 receptors (both β£ and β€) and binding of NF-kB to DNA were decreased by zinc deficiency in HUT-78. In HL-60, a monocytic-macrophage cell line, zinc deficiency increased production and gene expression of TNF-β£, IL-1β€ and IL-8. These cytotoxic cytokines are known to produce increased free radicals. Thus zinc may function as an important antioxidant. In conclusion, decreased production of IL-2 in zinc deficiency may be due to decreased activation of NF-kB and subsequent decreased gene expression of IL-2 and IL-2 receptor β£. Our studies show that zinc deficiency affects cell-mediated immunity and leads to activation of monocytes-macrophages and may play an important role as an antioxidant.