期刊連結：http://www.gouthyperuricemia.com

Purpose: Not all subjects with hyperuricemia have gout arthritis; it is well known that gouty inflammation plays a key role in gout disease. Here, we summarize gouty inflammation, which includes phagocytosis of monosodium urate (MSU) crystals, NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, interleukin-1β (IL-1β) release, neutrophilic recruitment and gouty resolution.
Findings: Toll-like receptor-2 (TLR-2), TLR-4, myeloid differentiation primary response 88 (MyD88), cGMP-dependent protein kinase 2 (cGKII) and lipid sorting were recognized as major routes for MSU phagocytosis. After MSU phagocytosis, activation of NLRP3 inflammasome is needed to evoke further gouty inflammation. The NLRP3 inflammasome is composed of Caspase-1, apoptosis-associated speck-like protein containing CARD (ASC) and NLRP3, which is activated through ion channel, lysosome rupture and reactive oxygen species (ROS) models. The activation may involve changes in extracellular ATP concentration, K+ efflux, lysosome rupture, release of lysosomal protein cathepsin B and change of ROS concentration in the cell. Leukotriene B4 act as an intermediary molecule linking MSU and NLRP3 inflammasome activation to release IL-1β. Before release of IL-1β, synthesis of pro-IL-1β and activation of NLRP3 inflammasome is required. Release of IL-1β causes neutrophilic recruitment to the joint to amplify the inflammatory syndrome. Gouty inflammation may progress into resolution a few days after initiation of gouty attack, which releases many cytokines or chemokines such as transforming growth factor beta1 (TGF-β1), tumor necrosis factor alpha (TNF-α) and suppressor of cytokine signaling family (SOCS family) to alleviate gouty syndrome.
Conclusion: The process of gouty inflammation is an independent factor from hyperuricemia, and phagocytosis of MSU and activation of NLRP3 inflammasome are the key initiators for gouty inflammation.