The role of the NLRP3 inflammasome in gout

Abstract

Gout is an inflammatory arthritis characterized by abrupt self-limiting attacks of inflammation caused by precipitation of monosodium urate crystals (MSU) in the joint. Recent studies suggest that orchestration of the MSU-induced inflammatory response is dependent on the proinflammatory cytokine IL-1β, underlined by promising results in early IL-1 inhibitor trials in gout patients. This IL-1-dependent innate inflammatory phenotype, which is observed in a number of diseases in addition to gout, is now understood to rely on the formation of the macromolecular NLRP3 inflammasome complex in response to the MSU ‘danger signal’. This review focuses on our current understanding of the NLRP3 inflammasome and its critical role in MSU-crystal induced inflammatory gout attacks. It also discusses the management of treatment-resistant acute and chronic tophaceous gout with IL-1 inhibitors; early clinical studies of rilonacept (IL-1 Trap), canakinumab (monoclonal anti-IL-1β antibody), and anakinra have all demonstrated treatment efficacy in such patients.

Keywords:

• gout
• inflammasome
• NLRP3
• IL-1

Acknowledgments

SR Kingsbury and PG Conaghan are supported by the Leeds Musculoskeletal Biomedical Research Unit and Arthritis Research UK, and MF McDermott by FP7-HEALTH-2007-2.4.4-1 grant and Arthritis Research UK.

Disclosure

The authors report no conflicts of interest in this work.