Department of Pathology, UMass Medical School, S2-109, 55 Lake Avenue North, Worcester, MA 01655, USA. kenneth.rock@ umassmed.edu
Nat Rev Rheumatol. 2013 Jan;9(1):13-23. doi: 10.1038/nrrheum.2012.143. Epub 2012 Sep 4.
Uric acid is a waste product of purine catabolism. This molecule comes to clinical attention when it nucleates to form crystals of monosodium urate (MSU) in joints or other tissues, and thereby causes the inflammatory disease of gout. Patients with gout frequently suffer from a number of comorbid conditions including hypertension, diabetes mellitus and cardiovascular disease. Why MSU crystals trigger inflammation and are associated with comorbidities of gout has been unclear, but recent studies provide new insights into these issues. Rather than simply being a waste product, uric acid could serve a pathophysiological role as a local alarm signal that alerts the immune system to cell injury and helps to trigger both innate and adaptive immune responses. The inflammatory component of these immune responses is caused when urate crystals trigger both inflammasome-dependent and independent pathways to generate the proinflammatory cytokine IL-1. The resulting bioactive IL-1 stimulates the inflammation of gout and might contribute to the development of other comorbidities. Surprisingly, the same mechanisms underlie the inflammatory response to a number of irritant particles, many of which also cause disease. These new insights help to explain the pathogenesis of gout and point to potential new therapeutic targets for this and other sterile inflammatory diseases.
尿酸是嘌呤代谢的废物产物。当这种分子在关节或其他组织中凝聚形成单钠尿酸盐 (MSU) 晶体时，它就会引起痛风的炎症性疾病，从而引起临床关注。痛风患者经常患有多种合并症，包括高血压、糖尿病和心血管疾病。为什么 MSU 晶体引发炎症，与痛风的合并症有关，这一直不清楚，但最近的研究为这些问题提供了新的见解。尿酸不仅仅是一种废物产物，它可能作为一种局部报警信号发挥病理生理作用，提醒免疫系统细胞损伤，并有助于触发先天和适应性免疫反应。尿酸晶体引发炎症小体依赖和独立途径产生促炎细胞因子 IL-1 时，会引起这些免疫反应的炎症成分。由此产生的生物活性 IL-1 刺激痛风的炎症，并可能导致其他合并症的发展。令人惊讶的是，许多同样的机制也与许多刺激性颗粒的炎症反应有关，这些颗粒也会导致疾病。这些新的见解有助于解释痛风的发病机制，并为这种疾病和其他无菌性炎症性疾病指出潜在的新治疗靶点。
