What is it about?

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.

Featured Image

Why is it important?

This review discusses the role of innate immunity and NLRP3 inflammasome activation in gout

Perspectives

The impressive results of IL-1 inhibitors for the treatment of autoinflammatory syndromes confirm the potential of these agents for diseases such as gout, which involve excessive IL-1β production. Despite significant advances in our understanding of the inflammatory processes involved in an acute gout attack, many questions remain to be addressed. The precise mechanism by which crystal recognition is achieved remains elusive, whilst the role of additional cytokines, which may be activated by the NLRP3 inflammasome, such as IL-18, must also be evaluated. Moreover, MSU may trigger other pathways aside from the NLRP3 inflammasome and it will be important to identify such pathways and understand their interaction with the NLRP3 inflammasome and IL-1β production in the acute and resolution phases of gout. Answers to these questions will no doubt provide important insights into the mechanisms underlying MSU-induced inflammation and resolution, but may also reveal novel biologically relevant targets for the development of new, more effective therapeutic options for the treatment of gout.

Professor Michael McDermott
University of Leeds

Read the Original

This page is a summary of: The role of the NLRP3 inflammasome in gout, Journal of Inflammation Research, March 2011, Taylor & Francis, DOI: 10.2147/jir.s11330.
You can read the full text:

Read

Contributors

The following have contributed to this page