The Role of Monocytes in Gouty Arthritis

Gout is one of the most painful forms of arthritis characterised by the deposition of monosodium urate crystals (MSU) in the joint synovium and the subsequent acute influx of circulating leukocytes. This study investigated the contribution of the inflammatory microenvironment in driving recruited monocyte differentiation and function in acute gouty inflammation. Using the murine peritoneal model of MSU-induced inflammation, the differentiation and functional phenotypes of MSU-recruited monocytes were compared in normal acute inflammation and in an inflammatory environment depleted of resident macrophages and infiltrating neutrophils. In addition, the role of the local environment in producing monocyte chemoattractant protein-1 (MCP-1) was investigated. Furthermore, the effect of transmigration on the suppressor phenotype of recruited monocytes was also explored. The pro-inflammatory environment was shown to play a key role in the differentiation and function of recruited monocytes in MSU-induced acute inflammation. In addition, infiltrating neutrophils suppressed the pro-inflammatory abilities of recruited monocytes, which may contribute to the resolution of inflammation. Using both whole peritoneal membrane preparations and in vitro culture techniques, results showed that mesothelial cells lining the peritoneal membrane were a source of MCP-1 production, which contributed to monocyte recruitment. Finally no differences were observed in either the differentiation or functional phenotypes of MSU-recruited monocytes isolated from Glatiramer acetate (GA) treated or non-treated mice. These findings suggest that the inflammatory microenvironment plays a key role in driving the recruitment, differentiation and function of circulating monocytes in the MSU-induced model of acute inflammation.