Formation of MSU crystals may also occur in the blood from hyperuricemic patients 22. Deposition of MSU crystals can also occur in other tissues and organs in humans, although it is reported seldom 20, 21, 22. Precipitation of uric acid into monosodium urate (MSU) crystals in joints elicits acute aseptic inflammation, the gouty arthritis, prevalence of which increases with increasing SUA levels 19.

This is due to multiple missense mutations in the uricase enzyme responsible for degrading UA to a more soluble allantoin in most other species. In humans, the concentration of uric acid (UA) can reach its theoretical supersaturation threshold in extracellular fluids. Some studies have found SUA to be an independent cardiovascular risk factor 1, 4, 5, 7, 14, but others did not 15, 16, 17, 18.

Hyperuricemia is also a common problem after renal, liver and cardiac transplantation 13.Įpidemiological studies are conflicting whether elevated serum uric acid (SUA) is an independent risk factor for cardiovascular disease. Hyperuricemia is a modifiable condition that can lead to gout, and may be an independent risk factor for mortality 1, renal disease 2, 3, cardiovascular events 4, 5, 6, 7, cancer 8, 9, hypertension 10, 11, and diabetes 12. Soluble UA is internalized in blood cells but does not potentiate or reduce LPS-induced release of cytokines. We show that crystallized, but not soluble, UA induces production of pro-inflammatory mediators in human whole blood. 14C labeled UA was used to assess intracellular uptake of UA. RT-qPCR and multiplex bead based immunoassay were used to measure mRNA expression and cytokine release at 2 and 4 h of culture, respectively. 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). We aimed to explore the net effects of experimentally rising SUA in human whole blood cultures on several mediators of inflammation. On the other hand, soluble uric acid possesses antioxidant properties that might attenuate inflammatory responses. 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. 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.

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