Uric acid, a nucleic acid degradation product, down-regulates dsRNA-triggered arthritis

Abstract: Uric acid, the naturally occurring deg-radation product of purine metabolism, is a danger signal, driving maturation of dendritic cells. It is well known that uric acid crystals display potent proinflammatory properties—the cause of gout— whereas the biological properties of soluble uric acid are less well documented. We have demon-strated previously that nucleic acids of endogenous and exogenous origin display proinflammatory properties. The aim of the present study was to assess the impact of soluble uric acid on in vivo inflammatory responses. Mice were administered with uric acid suspension in saline or saline alone prior to induction of neutrophil-mediated inflam-mation, delayed-type hypersensitivity, histamin-in-duced edema (measure of vasodilation capacity), as well as double-stranded (ds)RNA-triggered arthri-tis. Frequency and severity of arthritis were de-creased significantly in mice exposed to dsRNA and simultaneously treated with uric acid as compared with saline-treated controls. Also, granulocyte-me-diated inflammatory response and vasodilation ca-pacity were reduced significantly in mice treated with uric acid as compared with their control group. The data suggest that down-regulation of inflammation was mediated by skewing the inflam-matory response from the peripheral sites to the peritoneal cavity and down-regulating vasodilata-tory capacity and thereby affecting leukocyte mi-gration. In contrast, the T cell-mediated delayed-type hypersensitivity reaction was not affected sig-nificantly in mice exposed to uric acid. These findings demonstrate that uric acid displays a po-tent, distant anti-inflammatory effect in vivo. This property seems to be mediated by down-regulation of neutrophil influx to the site of inflammator