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.
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
Correspondence to Professor Leo A.B. Joosten, Radboudumc, Department of Internal Medicine, Route 463, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. Tel: +31 0243613283; e-mail: firstname.lastname@example.org