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.