Metabolic activation, indirect immunotoxicity, immunotoxic intermediates

It is generally accepted that the immune system is one of the major target organs for many toxic chemicals, and that many toxic chemicals require metabolic activation by cytochrome P450s for their toxicity. Although the immune cells possess a limited drug-metabolizing capacity, metabolic activation of certain toxicants in the liver and immune organs may have a significant role in chemical-induced immunosuppression. Although there is sufficient evidence for  metabolitesactivating immunocompetent cells by hapten-carrier formation this is not within the scope of this chapter. This chapter exclusively addresses the question of immunosuppressive effects of metabolites. To detect immunotoxicants requiring metabolic activation by cytochrome P450s in vivo, isozyme-selective inducers and inhibitors have been developed. For in vitro detection of immunotoxicants, cell-free systems and a coculture system...