A University of Toronto professor is proposing two new concepts to help better understand the cause of adverse drug reactions.
Jack Uetrecht of the Faculty of Pharmacy says that the leading theory on the cause of these reactions -- that the drug irreversibly binds to proteins or other large molecules which are then perceived as foreign and induce an immune response -- doesn't explain many of the key features of such reactions, including why the response only produces symptoms in some people.
He suggests that researchers consider the "danger hypothesis," which states that the immune system only responds to foreign substances if they appear to cause some sort of damage leading to a danger signal, rather than sticking to the traditional view that the immune system will attack anything foreign. Uetrecht says that researchers should also look at the innate immune system and not just focus on the more specific adaptive immune system. The innate system, which is associated with more primitive organisms but also present in humans, doesn't produce antibodies to foreign substances so if a drug causes cell damage it could provoke a response without leaving any of the evidence that researchers usually associate with an immune response.
"These concepts have the potential to lead to a better understanding of hypersensitivity reactions which in turn could lead to the development of tests to predict which drugs will be associated with such reactions, and as well which patients are likely to react to particular drugs," says Uetrecht.
The research, which was supported by the Medical Research Council of Canada, is published in the May issue of Chemical Research in Toxicology.
Journal
Chemical Research in Toxicology