Neutrophils play an essential role in host defense and sterile inflammation. Neutrophil dysfunction is a hallmark of acquired immunodeficiency during renal disease. Researchers hypothesized that neutrophil dysfunction might be explained by reduced renal clearance of the intrinsic purine metabolite soluble uric acid (sUA). 

Indeed, utilizing intravital microscopy and an air pouch paradigm, hyperuricemia (HU, serum UA of 9-12 mg/dL) linked or unrelated to renal failure dramatically reduced neutrophil adherence and extravasation with crystal- and coronavirus-associated sterile inflammation. This defective neutrophil recruitment may be partially reversed by depleting UA with rasburicase. The findings were verified in vitro using neutrophils or serum from individuals with renal dysfunction–related HU with or without UA depletion, which partially restored migratory neutrophil defects. sUA inhibited β2 integrin activity and internalization/recycling through modulating intracellular pH and cytoskeletal dynamics, which are known to influence neutrophil migratory and phagocytic capabilities. 

This impact was completely reversed by limiting intracellular absorption of sUA via urate transporters. In contrast, sUA showed no influence on neutrophil extracellular trap formation in either healthy or kidney-dysfunctional neutrophils. The findings showed that the intrinsic purine metabolite sUA has an unanticipated immunoregulatory role, in contrast to the well-known immunostimulatory effects of crystalline UA. Targeting UA specifically may assist in overcoming some kinds of immunodeficiency, such as renal disease, but it may also aggravate sterile forms of inflammation.