A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study

PLoS One. 2017 Aug 7;12(8):e0181100. doi: 10.1371/journal.pone.0181100. eCollection 2017.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01323335.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Biomarkers / blood
  • Double-Blind Method
  • Female
  • Gene Expression / drug effects
  • Humans
  • Inflammation / blood
  • Interleukin-6 / blood*
  • Lipids / administration & dosage
  • Male
  • Microarray Analysis
  • Middle Aged
  • Pilot Projects
  • Urate Oxidase / pharmacology*
  • Uric Acid / blood*
  • Uric Acid / pharmacology*

Substances

  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • Lipids
  • rasburicase
  • Uric Acid
  • Urate Oxidase

Associated data

  • ClinicalTrials.gov/NCT01323335

Grant support

This study was entirely funded by the National Institute on Aging intramural research Program. The drug rasburicase was donated by Sanofi-Synthelabo, Inc.