The roles of drug metabolism in the pathogenesis of T-cell-mediated drug hypersensitivity

Sidonie Nelly Lavergne, Brian Kevin Park, Dean John Naisbitt

Research output: Contribution to journalReview article

Abstract

PURPOSE OF REVIEW: The purpose of this review is to highlight recent studies on drug metabolism in T-cell-mediated reactions. Although the hapten theory and the danger hypothesis imply an important role of reactive metabolites in the pathogenesis of drug hypersensitivity, the more recent pi concept gives the central role to the parent drug. It is therefore important to have a broad vision on data supporting each theory to understand the potential role(s) of drug metabolism in T-cell-mediated hypersensitivity. RECENT FINDINGS: Reactive metabolites have been identified for most drugs associated with hypersensitivity. Recent studies have further characterized drug metabolism outside the liver, in key tissues such as the skin and immune cells. Localized drug metabolism is associated with oxidative stress, adduct formation and toxicity creating danger signals for antigen presenting cells, influencing whether a drug antigen will induce tolerance or immunity. SUMMARY: The involvement of metabolic drug activation in the initiation and propagation of hypersensitivity is intriguing since metabolites are generated in different quantities throughout the body, can be directly or indirectly toxic to cells, might stimulate innate immunity, and can bind to protein to generate neoantigens for cellular and humoral responses.

Original languageEnglish (US)
Pages (from-to)299-307
Number of pages9
JournalCurrent Opinion in Allergy and Clinical Immunology
Volume8
Issue number4
DOIs
StatePublished - Aug 1 2008

Keywords

  • Cytotoxicity
  • Danger signal
  • Drug metabolites
  • Drug metabolizing enzymes
  • Drug?protein adducts
  • Hapten theory
  • Oxidative stress
  • Pharmacogenomics
  • Pi concept
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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