Inflammation in gout: mechanisms and therapeutic targets


Key Points

  • Inflammatory cytokines, in particular IL-1β, are the key mediators of gouty inflammation

  • The NLRP3 inflammasome is the major pathway by which MSU crystals trigger the cellular inflammatory response

  • Multiple regulatory pathways modulate the activity of the inflammasome and the release of IL-1β; this may explain in part the clinical origins of gouty inflammation

  • Diet influences hyperuricaemia as well as the inflammatory state of macrophages in gout

  • Nutrients can modulate inflammasome activity and IL-1β release and participate in the regulation of pro-inflammatory as well as anti-inflammatory pathways in gout

  • The resolution of gouty inflammation is regulated at the cellular level as well as at the level of activation of the inflammasome; these pathways provide promising new avenues for therapeutic intervention


The acute symptoms of gout are triggered by the inflammatory response to monosodium urate crystals, mediated principally by macrophages and neutrophils. Innate immune pathways are of key importance in the pathogenesis of gout, in particular the activation of the NLRP3 inflammasome, which leads to the release of IL-1β and other pro-inflammatory cytokines. The orchestration of this pro-inflammatory cascade involves multiple intracellular and extracellular receptors and enzymes interacting with environmental influences that modulate the inflammatory state. Furthermore, the resolution of inflammation in gout is becoming better understood. This Review highlights recent advances in our understanding of both positive and negative regulatory pathways, as well as the genetic and environmental factors that modulate the inflammatory response. Some of these pathways can be manipulated and present novel therapeutic opportunities for the treatment of acute gout attacks.

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Figure 1: NLRP3 inflammasome activation by monosodium urate crystals.
Figure 2: IL-1 signalling links inflammasome activation with inflammatory cascades.
Figure 3: Checks and balances of gouty inflammation.
Figure 4: Therapeutic targets in gouty inflammation.


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The work of supported by a grant from the Swiss National Science Foundation (310030_173152).

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Both authors researched data and made a substantial contribution to discussion of the content and writing the article, and reviewed or edited the manuscript before submission.

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Correspondence to Alexander K. So.

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Competing interests

A.K.S. declares that he has acted as a consultant for AstraZeneca, Menarini and Novartis. F.M. declares no competing interests.

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Autoinflammatory disease

Inflammatory diseases not due to infections or injuries, mostly caused by malfunction in the innate immune system.


A multiprotein cytoplasmic complex that activates one or more inflammatory caspases, such as caspase-1, leading to the processing and secretion of the pro-inflammatory cytokines IL-1β and IL-18, and the processing and activation of factors triggering pyroptosis such as gasdermin D.


Inflammatory form of cell death mediated by inflammatory caspases such as caspase-1 and caspase-11 that results in the extracellular release of cellular content, including inflammatory mediators and danger signals.

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So, A., Martinon, F. Inflammation in gout: mechanisms and therapeutic targets. Nat Rev Rheumatol 13, 639–647 (2017).

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