Allergy and Chronic Toxicity Model Systems

Abstract

This chapter considers two extremes in the biological response to bioactive principles. On the one hand, there is the almost instantaneous effect of an allergen which can induce a hypersensitivity cascade leading to a potent reaction by the immune system. Such a reaction can lead to anaphylaxis and can be life threatening. Clearly the direct assay of allergens in susceptible individuals cannot be safely carried out so model systems have been developed. These range from the very simple (antibody binding) tests to more complex systems which monitor the degranulation reaction of sensitised mast cells. At the other extreme, compounds administered at a level where they display chronic toxicity are also difficult to assess directly in individuals. The long-term effect can take a considerable time to develop and it is neither practical nor useful to carry out ‘lifetime exposure’ reactions. Once again model systems are required. In this chapter, we consider two human cell-based model systems that can be used for the assessment of immediate and chronic toxins. The relevance of cell culture systems in the measurement of bioactivity is investigated, leading to a view being developed of the importance of escalation and extrapolation in bioactivity measurement. The chapter concludes by revisiting the concepts of simplicity and complexity in living systems.