Crystallized but not soluble uric acid elicits pro-inflammatory response in short-term whole blood cultures from healthy men

• Published in: Scientific Reports
• Main Authors: Brovold, Henrik, Lund, Trine, Svistounov, Dmitri, Solbu, Marit Dahl, Jenssen, Trond Geir, Ytrehus, Kirsti, Zykova, Svetlana
• Format: Report
• Language: English
• Published: Springer Nature 2019
• Subjects: Andreassen; Arctic; Norway; Steinnes; Tromsø; Arctic University of Norway; UiT The Arctic University of Norway
• Online Access: http://hdl.handle.net/11250/2634513; https://doi.org/10.1038/s41598-019-46935-w

Several epidemiological studies have pointed at serum uric acid (SUA) as an independent risk factor for mortality, diabetes, hypertension, cardiovascular and kidney disease; however, no clear pathogenic pathway is established. Uric acid (UA) crystals show pro-inflammatory properties and can thus create or contribute to the state of chronic low-grade inflammation, a widely accepted pathogenic mechanism in several of the above-mentioned pathologies. On the other hand, soluble uric acid possesses antioxidant properties that might attenuate inflammatory responses. We aimed to explore the net effects of experimentally rising SUA in human whole blood cultures on several mediators of inflammation. production of tNF-α, IL-1ß, IL-1RA, MCP-1 and IL-8 was assessed upon addition of 200 μM UA, 500 μM UA or monosodium urate (MSU) crystals in the presence or absence of 5 ng/ml lipopolysaccharide (LPS). RT-qPCR and multiplex bead based immunoassay were used to measure mRNA expression and cytokine release at 2 and 4 h of culture, respectively. 14C labeled UA was used to assess intracellular uptake of UA. We show that crystallized, but not soluble, UA induces production of pro-inflammatory mediators in human whole blood. Soluble UA is internalized in blood cells but does not potentiate or reduce LPS-induced release of cytokines. Crystallized but not soluble uric acid elicits pro-inflammatory response in short-term whole blood cultures from healthy men The authors thank Gro Bolstad for technical assistance, Trine Kalstad for help with Bio-Plex multiplex analysis, Thomas Vennø Andreassen for advice and technical assistance, Knut Steinnes for technical assistance. The publication charges for this article have been funded by a grant from the publication fund of UiT - The Arctic University of Norway. The study has been funded by the UiT – The Arctic University of Norway and the Tromsø Research Foundation (grant nr 311333/A22349). publishedVersion