Tanaka Toshiko, Milaneschi Yuri, Zhang Yongqing, Becker Kevin G, Zukley Linda, Ferrucci Luigi
Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland, United States of America.
Department of Psychiatry, Amsterdam Public Health, VU University Medical Center, Amsterdam, The Netherlands.
PLoS One. 2017 Aug 7;12(8):e0181100. doi: 10.1371/journal.pone.0181100. eCollection 2017.
Uric acid has been linked with increased risk of chronic disease such as cardiovascular disease and this association has been attributed to a pro-inflammatory effect. Indeed, observational studies have shown that high uric acid is associated with high level of pro-inflammatory cytokines in the blood. However, whether high uric acid directly affects inflammation or rather represents a parallel defensive antioxidant mechanism in response to pathology that causes inflammation is unknown. To determine whether acute increase or decrease uric acid levels affects inflammation in healthy individuals, a randomized, placebo-controlled, double blind clinical study of uric acid or rasburicase with 20 healthy volunteers in each treatment-placebo group was conducted at the National Institute on Aging (NIA) Clinical Research Unit (CRU) at Harbor Hospital in Baltimore, MD. Change in inflammatory response was assessed by administering an oral lipid tolerance before and after the treatment of uric acid, rasburicase and placebo. Following uric acid administration, there was an accentuated increase in IL-6 during the oral lipid tolerance test (P<0.001). No significant differences were observed after lowering of uric acid with rasburicase. No side effects were reported throughout the trial. In health individuals, acute increase in uric acid results in an increased IL-6 response when challenged with lipid load. Such effect of amplification of inflammatory response may explain the higher risk of chronic diseases observed in subclinical hyperuricemia in observational studies.
ClinicalTrials.gov NCT01323335.
尿酸与心血管疾病等慢性疾病风险增加有关，这种关联归因于促炎作用。确实，观察性研究表明高尿酸与血液中促炎细胞因子水平升高有关。然而，高尿酸是直接影响炎症，还是代表对引起炎症的病理状态的一种平行防御抗氧化机制尚不清楚。为了确定尿酸水平的急性升高或降低是否会影响健康个体的炎症，在马里兰州巴尔的摩港医院的国立衰老研究所（NIA）临床研究单位（CRU）对尿酸或重组尿酸氧化酶进行了一项随机、安慰剂对照、双盲临床研究，每个治疗 - 安慰剂组有20名健康志愿者。在尿酸、重组尿酸氧化酶和安慰剂治疗前后，通过口服脂质耐量试验评估炎症反应的变化。给予尿酸后，口服脂质耐量试验期间白细胞介素 - 6（IL - 6）有明显升高（P<0.001）。用重组尿酸氧化酶降低尿酸后未观察到显著差异。整个试验期间未报告副作用。在健康个体中，尿酸急性升高会导致在脂质负荷刺激时IL - 6反应增加。炎症反应放大的这种效应可能解释了观察性研究中在亚临床高尿酸血症中观察到的慢性疾病风险较高的现象。
ClinicalTrials.gov NCT01323335。
