Factors modulating the inflammatory response in acute gouty arthritis

Curr Opin Rheumatol. 2017 Mar;29(2):163-170. doi: 10.1097/BOR.0000000000000366.

Abstract

Purpose of review: Gout is a common debilitating form of arthritis and despite our extensive knowledge on the pathogenesis its prevalence is still rising quickly. In the current review, we provide a concise overview of recent discoveries in factors tuning the inflammatory response to soluble uric acid and monosodium urate crystals.

Recent findings: It appears that soluble uric acid has a much larger role to play than just being a risk factor for gout. It may have widespread consequences for systemic inflammation and the development of metabolic syndrome. Additionally, a specific gout-related gut microbiome might not only provide us with a new diagnostic tool, but also highlights possible new therapeutic targets. Furthermore, several recent publications further elucidated the roles of mitochondrial dysfunction, production of reactive oxygen species, autophagy, and AMP-dependent protein kinase in monosodium urate-induced NLRP3 inflammasome activation. Finally, neutrophils have been shown to be involved in both the promotion and resolution of gouty inflammation. A new alpha-1-antitrypsin fusion protein may limit the proinflammatory effects of neutrophil-derived serine proteases.

Summary: Together, these studies provide us with many new insights in the pathogenesis of gout, important new treatment targets, and a rationale to further study the role of soluble uric acid in inflammatory diseases.

Publication types

  • Review

MeSH terms

  • Arthritis, Gouty / immunology*
  • Autophagy / immunology
  • Gastrointestinal Microbiome / immunology*
  • Gout / immunology
  • Humans
  • Hyperuricemia / immunology*
  • Inflammasomes / immunology
  • Inflammation
  • Mitochondria / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology
  • Neutrophils / immunology
  • Oxidative Stress
  • Phosphotransferases (Phosphate Group Acceptor) / immunology
  • Reactive Oxygen Species / immunology
  • Uric Acid / immunology*

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Reactive Oxygen Species
  • Uric Acid
  • AMP-dependent kinase (ATP-forming)
  • Phosphotransferases (Phosphate Group Acceptor)