Toxic effect of zinc on NF-κB, IL-2, IL-2 receptor α, and TNF-α in HUT-78 (Th0) cells

Zinc deficiency decreased cellular immune response. Zinc supplementation reverses this response. High concentration of zinc intake is reported to alter immune response. We hypothesize that higher concentration of zinc adversely affects T-cell immune response. In this study, we examined whether higher concentration of zinc affects expression of IL-2, IL-2R alpha, and TNF-alpha, and NF-kappa B activation in HUT-78 (Th-0) cells. The results show that HUT-78 cells incubated in 15, 50, and 100 mu M zinc medium had significantly higher intracellular zinc contents and faster growth after 4 days of incubation, compared to the cells incubated in I mu M zinc medium. After PMA/PHA stimulation, I mu M zinc showed significant decreases in NF-kappa B activation, and in the levels of IL-2, IL-2R alpha, and TNF-alpha production and mRNAs compared to 15 mu M zinc. The cells incubated in higher concentrations of zinc (50 and 100 mu M zinc) showed mild to moderate decreases in the levels of IL-2, IL-2R alpha, and TNF-a production and mRNAs, and in NF-KB activation compared to those incubated in 15 mu M zinc medium. These data indicate that not only low level of zinc, but also high levels of zinc decrease Th1 function. (c) 2006 Elsevier Ireland Ltd. All rights reserved.