Mechanisms of Drug-Induced Allergy

Schnyder, Benno; Pichler, Werner J.
March 2009
Mayo Clinic Proceedings;Mar2009, Vol. 84 Issue 3, p268
Academic Journal
We identified English-language publications on hypersensitivity reactions to xenobiotics through the PubMed database, using the search terms drug and/or xenobiotic, hypersensitivity reaction, mechanism, and Immune mediated. We analyzed articles pertaining to the mechanism and the role of T cells. immune hypersensitivity reactions to drugs are mediated predominantly by lgE anti bodies or T cells. The mechanism of lgE-mediated reactions is well investigated, but the mechanisms of T-cell-mediated drug hyper-sensitivity are not well understood. The literature describes 2 concepts: the hapten/prohapten concept and the concept of pharmacological interactions of drugs with immune receptors, in T-cell-mediated allergic drug reactions, the specificity of the T-cell receptor that is stimulated by the drug may often be directed to a cross-reactive major histocompatibility complex-peptide compound. Thus, previous contact with the causative drug is not obligatory, and an immune mechanism should be considered as the cause of hypersensitivity, even in reactions that occur on primary exposure, indeed, immune-mediated reactions to xenobiotics in patients without prior exposure to the agent have been described recently for radiocontrast media and neuromuscular blocking agents. Thus, the "allergenic" potential of a drug under development should be evaluated not only by screening its haptenlike characteristics but also by assessing its direct lmmunostimulatory potential.


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