title: Activation of inflammasomes by agents causing idiosyncratic skin reactions: a possible biomarker.
abstract: Chemically reactive drugs and drugs that form reactive metabolites often cause idiosyncratic drug reactions (IDRs); however, not all such drugs are associated with IDRs. Most IDRs appear to be immune mediated; therefore, the ability of a drug to induce an immune response may be the determinant of which drugs will cause IDRs. Inflammasome activation plays an important role in the initiation of an immune response. In this study, we studied two pairs of similar chemically reactive drugs, telaprevir/boceprevir and dimethyl fumarate/ethacrynic acid. In both pairs, the drug associated with skin reactions activated inflammasomes in THP-1 cells, and the drug not associated with skin reactions did not.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, and ‡Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto , Toronto, Ontario M5S 3M2, Canada.
authors.forename: J Kyle
authors.initials: JK
authors.lastname: Weston
authors.forename: Jack
authors.initials: J
authors.lastname: Uetrecht
mesh_terms: D015415:Biomarkers; D002460:Cell Line; D000069462:Dimethyl Fumarate; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions / Q000276:immunology*; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005650:Fumarates / Q000494:pharmacology*; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects* / Q000276:immunology; D015394:Molecular Structure; D009842:Oligopeptides / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D013329:Structure-Activity Relationship
chemical_list: D015415:Biomarkers; D005650:Fumarates; D058847:Inflammasomes; D009842:Oligopeptides; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; D000069462:Dimethyl Fumarate; D004976:Ethacrynic Acid