Patients with naproxen-induced liver injury display T-cell memory responses toward an oxidative (S)-O-desmethyl naproxen metabolite but not the acyl glucuronide.
T lymphocytes
drug-induced liver injury
human
immune system
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
revised:
30
05
2023
received:
24
03
2023
accepted:
13
06
2023
medline:
2
1
2024
pubmed:
29
7
2023
entrez:
29
7
2023
Statut:
ppublish
Résumé
Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (IBU) and naproxen (NAP) is associated with idiosyncratic drug-induced liver injury (DILI). Carboxylate bioactivation into reactive metabolites (e.g., acyl glucuronides, AG) and resulting T-cell activation is hypothesized as causal for this adverse event. However, conclusive evidence supporting this is lacking. In this work, we identify CD4 CD4 Our results confirm hepatic T-cell infiltrations in NSAID-induced DILI, and show a T-cell memory response toward DM-NAP indicating an immune-mediated basis for the adverse event. Whilst bioactivation at the carboxylate group is widely hypothesized to be pathogenic for NSAID associated DILI, we found no evidence of this with NAP.
Sections du résumé
BACKGROUND
BACKGROUND
Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (IBU) and naproxen (NAP) is associated with idiosyncratic drug-induced liver injury (DILI). Carboxylate bioactivation into reactive metabolites (e.g., acyl glucuronides, AG) and resulting T-cell activation is hypothesized as causal for this adverse event. However, conclusive evidence supporting this is lacking.
METHODS
METHODS
In this work, we identify CD4
RESULTS
RESULTS
CD4
CONCLUSION
CONCLUSIONS
Our results confirm hepatic T-cell infiltrations in NSAID-induced DILI, and show a T-cell memory response toward DM-NAP indicating an immune-mediated basis for the adverse event. Whilst bioactivation at the carboxylate group is widely hypothesized to be pathogenic for NSAID associated DILI, we found no evidence of this with NAP.
Substances chimiques
Naproxen
57Y76R9ATQ
Glucuronides
0
Anti-Inflammatory Agents, Non-Steroidal
0
Ibuprofen
WK2XYI10QM
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
200-214Subventions
Organisme : Medical Research Council
Pays : United Kingdom
Informations de copyright
© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
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