Small Chemicals, Bioactivation, and the Immune System – A Fragile Balance of i‐Tox and Benefits?

Abstract

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.

Present and future ofin vitroimmunotoxicology in drug development

“…Hyperthermic reactions (> 38.0-38.5°C) with chills, arthralgias, and malaise have been described in patients treated with immunostimulatory medicinal products or following the administration of vaccines and recombinant cytokines. Hypersensitivity reactions are (in industrialized countries) by far the most frequently reported immunotoxic effects of drugs and other chemicals in human beings (Esser and Jux, 2009 …”

Immunotoxicity and disease resistance in Japanese quail (Corturnix coturnix japonica) exposed to malathion

“…Effects of contaminants on wildlife species have become increasingly important, particularly in the areas of ecological risk assessment (Kendall and Smith 2003). Current reports suggest immunotoxic effect of environmental contaminants (Esser and Jux 2009;Grove et al 2009). Accumulation of environmental contaminants in soil and water, as well as bioaccumulation in prey species, can lead to disturbances in wildlife and even extinction of species (Hamlin and Guillette 2010).…”

Bioactivation of herbal constituents: simple alerts in the complex system

“…Therefore, inter-individual difference in immune response is a key factor influencing bioactivation-mediated herbal toxicity [140]. Some reductive substances (e.g., reduced glutathione), as natural trapping agents, play a key role in capturing reactive metabolites.…”