Value of animal models for predicting hypersensitivity reactions to medicinal products.
Although hypersensitivity reactions induced by medicinal products and chemicals are relatively common, few predictive models are available. A major difficulty is our currently limited understanding of the mechanisms involved, and efforts should be paid to better defining drug immunogenicity, hapten formation and immune effector mechanisms. A second difficulty is the multiplicity of clinical manifestations presumably due to varying mechanisms. Available models can only predict a few of these reactions. Anaphylaxis models in guinea-pigs can be only used for the safety assessment of macromolecules which are neither humanized or of human origin, whereas guinea-pig or mouse models can detect the majority of human contact sensitizers. In addition to the extensive validation of existing models, promising avenues of research are expected to be found in the use of novel animal models, particularly those using genetically modified animals, such as transgenic and knock-out mice.
Department of Pharmacology, Medical Toxicology and Environmental Medicine, et INSERM U98-X, Faculté de Médecine Lyon-RTH Laënnec, France.
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Choquet-Kastylevsky
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Descotes
D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000209:etiology; D006168:Guinea Pigs; D006801:Humans; D000922:Immunotoxins / Q000009:adverse effects*; D051379:Mice; D018345:Mice, Knockout; D015262:Xenobiotics / Q000009:adverse effects*
D000485:Allergens; D000922:Immunotoxins; D015262:Xenobiotics