Immunoregulation of natural and lymphokine-activated killer cells by selenium

The effect of selenium (Se) on natural killer (NK) and lymphokine-activated killer (LAK) cell activities and proliferative responses of human lymphocytes was studied in vitro. Direct addition of Se at 1.0 microgram/ml final concentration to the mixture of target and effector cells during a 4 h cytotoxicity assay significantly suppressed the NK activity of normal lymphocytes. When lymphocytes were preincubated with Se at concentrations as low as 0.2 microgram/ml for a period of 48 h, a significant inhibitory effect on NK activity was observed. In the LAK cell assay, direct addition of Se at concentrations of 0.2-1.0 microgram/ml to a mixture of target and effector cells did not show any effects on LAK cell activity, whereas LAK cells generated in the presence of Se at 0.8 microgram/ml showed significant inhibition of their functions. Lymphocyte proliferative responses to T cell mitogens such as phytohemagglutinin (PHA) and concanavalin A (Con A) were also significantly suppressed by direct addition of Se at 0.5-1.0 microgram/ml. The inhibitory effect of Se was not due to nonspecific toxicity of effector cells as demonstrated by viability nor was the effect directed against target cells. These studies suggest that although Se is an essential micronutrient for various immune mechanisms, an excess of Se may have a deleterious effect on certain immunological functions. As these activities are considered to be important defense mechanisms against tumors and virus infections, a nutritional imbalance of Se could result in an increased risk of these disorders.