AB0057 THE ROLE OF NON-INFLAMMATORY MACROPHAGES INITIATING AND RESOLVING THE INFLAMMATORY RESPONSE OF MONOSODIUM URATE IN MICE

Abstract

Background:Gout is the most common chronic inflammatory arthritis around the world which is associated with many conditions that affect longevity and well-being, such as metabolic syndrome, cardiovascular diseases, and renal diseases. [1]Objectives:Gout is the most common inflammatory arthritis around the world. Innate immunity has been implicated in gout inflammation in recent years. However, the phenomena of maintenance of ‘asymptomatic’ hyperuricemia, the spontaneous resolution of acute gouty arthritis and non-inflammatory tophus and its association with immune regulation are still elusive. We propose that resident macrophages may be a key player in the suppression of gouty inflammation. To address this hypothesis, we used non-inflammatory macrophages to explore the role played in initiating or resolving the inflammatory response.Methods:Bone marrow-derived macrophages (BMDM) were stimulated with monosodium rate (MSU), then analyzed the expression of RNA and protein of inflammatory cytokines, including IL-1β, IL-18 and TNF-α. In addition, we also observe the ability of macrophage to phagocyte and hydrolyze MSU crystal.Results:Our results indicate that MSU alone could not induce IL-1β, IL-18, and TNF-α mRNA expression and protein production. However, when macrophages were pre-stimulated with lipopolysaccharide (LPS) or MSU, as well as in combination the production of IL-1β and IL-18 were significantly increased. Furthermore, MSU maybe amplifies LPS-induced protein production of IL-1β and IL-18 but not in TNF-α. A temporal delay in the correlation between mRNA expression and protein production was shown. The results also indicated that macrophages could not only phagocytize MSU crystals but may also hydrolyze MSU crystals.Conclusion:These data indicate that MSU crystal alone is insufficient to induce pro-inflammatory cytokines production, however, when exposed to an infectious source of infection, it will amplify the inflammatory response and there is a synergistic effect between MSU and LPS. This may explain the diverse clinic phenomena of ‘asymptomatic’ hyperuricemia, non-inflammatory tophus and acute gouty arthritis. The high efficiency of phagocytosis and hydrolyzed MSU crystals of macrophages may explain the spontaneous regression of acute gouty arthritis. These findings may provide a new therapy for the prevention and treatment of acute gout attacks.