Immunotoxicology

Michael I Luster and Petia P Simeonova, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA

Dori R Germolec, Environmental Immunology Section, National Institute of Environmental Health Sciences, NIEHS, Research Triangle Park, North Carolina, USA

Copyright © 1998 Elsevier Ltd. All Rights Reserved.

Immunotoxicology has been defined as the study of adverse effects on the immune system resulting directly or indirectly from occupational, environmental or therapeutic exposure to chemicals (including drugs), biologic materials and, in certain instances, physiological factors, collectively referred to as agents. It encompasses studies of altered immunologic events associated with exposure of humans and wildlife species including immune regulation (suppression or enhancement), allergy and autoimmunity (Figure 1). In the former case, the systemic or local (e.g. skin, lung) immune system acts as a passive target for the agent, and the result may be an increased incidence or severity of infectious disease or neoplasia. In allergy, the immune system responds to chemical (hapten)-host protein conjugates or high molecular weight compounds. The most likely health consequences of the latter include respiratory tract allergies (e.g. asthma, rhinitis) or allergic contact dermatitis. Autoimmunity may occur either as a result of an agent-induced alteration in host tissue, endocrine function or immune regulation. More recently, studies in immunotoxicology have also included investigations into the role of inflammatory mediators, particularly cytokines and reactive oxygen species, in localized chemical toxicities as many of these mediators are produced by and/or act upon immune cells.

The potential for adverse health effects due to alterations in the immune system by toxic agents has been a matter of increasing scientific and public concern. As such, there have been marked efforts in both basic research undertaken within this area as well as development and incorporation of appropriate test methods to assess potential immunotoxicities in experimental animals, wildlife species and humans. Regarding resting methods, appropriate selection has been complicated by the need to employ distinct tests based upon the site examined (e.g. systemic, lung, skin) and the immunopathology of concern (i.e. hypersensitivity, immune regulation, autoimmunity, inflammation). However, our increased understanding of the molecular, cellular and genetic events responsible for mounting appropriate immune responses, as well as for the immune mediators involved in organ-specific necrotic and apoptotic processes, has provided opportunities for the utilization of more streamlined and informative tests for risk assessment and the development of novel preventive or therapeutic measures.

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