title: Factors modulating the inflammatory response in acute gouty arthritis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: aDepartment of Internal Medicine bRadboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands cDepartment of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Maartje C
authors.initials: MC
authors.lastname: Cleophas
authors.forename: Tania O
authors.initials: TO
authors.lastname: Crişan
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
mesh_terms: D015210:Arthritis, Gouty / Q000276:immunology*; D001343:Autophagy / Q000276:immunology; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D006073:Gout / Q000276:immunology; D006801:Humans; D033461:Hyperuricemia / Q000276:immunology*; D058847:Inflammasomes / Q000276:immunology; D007249:Inflammation; D008928:Mitochondria / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D018384:Oxidative Stress; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D014527:Uric Acid / Q000276:immunology*
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species; D014527:Uric Acid; C118888:AMP-dependent kinase (ATP-forming); D017856:Phosphotransferases (Phosphate Group Acceptor)