The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice

Abstract : Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints. Despite many treatment options for gout, there is a substantial need for alternative treatments for patients unresponsive to current therapies. Tyrosine kinase inhibitors have demonstrated therapeutic benefit in experimental models of antibody-dependent arthritis and in rheumatoid arthritis in humans, but to date, the potential effects of such inhibitors on gouty arthritis has not been evaluated. Here we demonstrate that treatment with the tyrosine kinase inhibitor imatinib mesylate (imatinib) can suppress inflammation induced by injection of MSU crystals into subcutaneous air pouches or into the ankle joint of wild type mice. Moreover, imatinib treatment also largely abolished the lower levels of inflammation which developed in IL-1R1-/- or KitW-sh/W-sh mice, indicating that this drug can inhibit IL-1-independent pathways, as well as mast cell-independent pathways, contributing to pathology in this model. Imatinib treatment not only prevented ankle swelling and synovial inflammation when administered before MSU crystals but also diminished these features when administrated after the injection of MSU crystals, a therapeutic protocol more closely mimicking the clinical situation in which treatment occurs after the development of an acute gout flare. Finally, we also assessed the efficiency of local intra-articular injections of imatinib-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles in this model of acute gout. Treatment with low doses of this long-acting imatinib:PLGA formulation was able to reduce ankle swelling in a therapeutic protocol. Altogether, these results raise the possibility that tyrosine kinase inhibitors might have utility in the treatment of acute gout in humans.
Type de document :
Article dans une revue
PLoS ONE, Public Library of Science, 2017, 12 (10), pp.e0185704. 〈10.1371/journal.pone.0185704〉
Liste complète des métadonnées

Littérature citée [20 références]  Voir  Masquer  Télécharger

http://hal.upmc.fr/hal-01622753
Contributeur : Gestionnaire Hal-Upmc <>
Soumis le : mardi 24 octobre 2017 - 16:17:09
Dernière modification le : mercredi 25 octobre 2017 - 09:49:35

Fichier

journal.pone.0185704.pdf
Publication financée par une institution

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Collections

Citation

Laurent Reber, Philipp Starkl, Bianca Balbino, Riccardo Sibilano, Nicolas Gaudenzio, et al.. The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice. PLoS ONE, Public Library of Science, 2017, 12 (10), pp.e0185704. 〈10.1371/journal.pone.0185704〉. 〈hal-01622753〉

Partager

Métriques

Consultations de la notice

67

Téléchargements de fichiers

19