Small chemicals, bioactivation, and the immune system--a fragile balance of i-tox and benefits?

Immunotoxicology concerns actions of chemicals which lead to adverse immune reactions. Current research challenges are the prediction of the immunotoxicologic risk potential of a chemical and a deeper mechanistic understanding of chemical-induced adverse immune reactions, to develop therapeutic or avoidance strategies. Small chemicals (SCs) can interfere with any cell type or function of the immune system. SCs are ubiquitous as food components, life-style products, or environmental pollutants. Besides their possible unspecific toxicity, they might form protein adducts, become part of recognized antigens, or they could be disruptors of immune signalling pathways. The incidence of autoimmune and allergic diseases has been rising over the last years, and evidence increases that SCs are important in this. Also, immunopharmacologists actively search for immunomodulating chemicals as urgently needed drugs. The aryl hydrocarbon receptor (AhR) is a SC-triggered transcription factor, and thus could link environmental signals to cellular responses. Recent research has shown a defined role for AhR in immunotoxicology. Here, we discuss concepts of SC immunotoxicity, and how AhR might be involved in adverse immune responses.