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Methods in Pharmacology and Toxicology 2014, pp 241-267
Date: 09 Apr 2014
Immunotoxicity- Thomas Hartung
- Abstract
Immunotoxicology has been discussed but little addressed in practice of toxicity testing over the last two decades. Current guidance relies on animal tests, which include some immune endpoints in repeated dose tests and call for dedicated tests only when certain alerts indicate a problem, which cannot be evaluated on the evidence obtained so far. At the same time, a wealth of in vitro approaches has been developed in basic and clinical immunology as well as pharmacological agent discovery, but little has been adopted for routine testing. The extent to which immunotoxicity of chemicals represents a health problem for the human population is not clear. It appears that responses of healthy individuals to immunological challenges differ widely and most immunomodulators have little adverse effects, except when coinciding with an infectious or malignant challenge, where the odds of progressing into infection and autoimmune diseases as well as cancer can be changed. The enormous overcapacity of immune defense and their fast restoration contribute to limiting health threats for the individual, though on a population level also minor immunomodulations might result in increased morbidities. In vitro alternative approaches might offer an opportunity to screen for problematic substances and prioritizing them for testing. New approaches emerge from mapping of pathways of immunotoxicity. Increasingly, the contribution of inflammatory and infectious components to the adverse outcome pathways of chemicals for various hazards is recognized, urging to include tests for proinflammatory and immunomodulatory properties into integrated testing strategies.