Immunopharmacology of hypersensitivity reactions to drugs

Drug hypersensitivity reactions are characterized by their unpredictability, lack of simple dose-dependency, host sensitivity, and potentially serious clinical outcome. They occur in a small proportion of patients, and usually the predisposing factors are unknown, although there is increasing evidence for genetic predisposition and disease being significant risk factors. The current understanding of the chemical basis of immune-mediated reactions is based on the hapten hypothesis, which requires drug bioactivation, covalent binding to proteins, followed by uptake, antigen processing, and a polyclonal immune response. The recently proposed "danger hypothesis" can be considered to be an essential addition to the hapten hypothesis. According to the danger hypothesis, the immune response to a drug-derived antigen requires the presence of co-stimulatory signals and cytokines, which propagate and determine the type of immune response. The "danger signal" might result from chemical, physical, or viral stress.