Role of natural killer cells in immunotoxicity: an update.

As natural killer cells play a significant role in innate immunity against viruses and neoplasia, the measurement of natural killer cell activity has long been recommended for nonclinical immunotoxicity evaluation. A number of agrochemical, industrial and environmental chemicals have been shown to impair natural killer cell activity. However, direct evidence for clinically significant pathologic consequences, such as infections or immunosuppression-related cancer in human beings exposed to these chemicals, is lacking. In addition, extremely few pharmaceuticals, including potent immunosuppressive drugs, have been shown to depress natural killer cell activity reproducibly. Due to this ambiguous situation, the value of measuring natural killer cell activity for the prediction of immunotoxicity is debatable, as reflected by recommendations included in recent guidelines for the nonclinical safety assessment of human pharmaceuticals. Limitations of current analyses of natural killer cell activity may explain this situation. Progress is expected from the utilization of most recent techniques to identify more relevant natural killer cell activation markers or from studying underlying mechanisms.