Uric acid, the naturally occurring degradation 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 demonstrated 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
inflammation, delayed-type
hypersensitivity, histamin-induced
edema (measure of vasodilation capacity), as well as double-stranded (ds)
RNA-triggered
arthritis. Frequency and severity of
arthritis were decreased significantly in mice exposed to dsRNA and simultaneously treated with
uric acid as compared with saline-treated controls. Also, granulocyte-mediated inflammatory response and vasodilation capacity 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 inflammatory response from the peripheral sites to the peritoneal cavity and down-regulating vasodilatatory capacity and thereby affecting leukocyte migration. In contrast, the T cell-mediated delayed-type
hypersensitivity reaction was not affected significantly in mice exposed to
uric acid. These findings demonstrate that
uric acid displays a potent, distant anti-inflammatory effect in vivo. This property seems to be mediated by down-regulation of neutrophil influx to the site of inflammatory insult.