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Immunotoxicology: An OverviewChemical Industry Institute of Toxicology, Department of Cell Biology, P.O. Box 12137, Research Triangle Park, North Carolina 27709
Chemical Industry Institute of Toxicology, Department of Cell Biology, P.O. Box 12137, Research Triangle Park, North Carolina 27709 It is now known that chemicals and drugs may induce selective toxicity which may alter the interactions between immunocompetent cells, especially if the toxicity occurs during proliferation and differentiation. Hence, a flexible panel of sensitive in vivo and in vitro assays has been developed and validated to assess the immunotoxicity or immunopharmacology of suspect agents in rodents. The combined use of such sequential analysis methods with host resistance assays can effectively define immunomodulation following exposure to xenobiotics. Methods development, refinement and validation will be an ongoing requirement because of our rapidly expanding knowledge of the cell biology of the immune system. Classic studies of the comparative preclinical toxicology of several immunosuppressive drugs have substantiated species similarities and have contributed significantly to the development of predictive rodent models for extrapolation to humans. Studies of immunopharmacology and immunotoxicity of cyclosporin A, for example, produced both the desired pharmacology and the undesired toxicity at similar doses in both rodents and humans. When species differences are observed during toxicology studies they are most probably due to differences in absorption, disposition, metabolism, excretion, or delivered dose at the target tissue, rather than major species differences in cellular targets or cell physiology. This assumption is the basis for using rodent species to predict the toxicity of chemicals and drugs under development. The next few years will present novel and exciting challenges to the field of toxicology as safety assessment issues emerge regarding the use of species-specific recombinant biologicals (e.g., growth hormones, interferons, interleukins, tumor necrosis factor, and defined vaccines), biological and biochemical pesticides (e.g., recombinant microbes), immunopharmacologically active drugs, and monoclonal antibody reagents designed as drug delivery or detoxification vehicles. These agents will require the thoughtful application of flexible toxicology protocols designed to reveal whether they are immunotoxic, immunopharmacologically active, or immunogenic. The design of such immunotoxicology studies will be based on an understanding of the potential targets within the immune system and the interactions of chemicals with immunocompetent cells.
Toxicologic Pathology, Vol. 15, No. 3,
265-271 (1987) |
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