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

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...

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Autores principales: Tanaka, Toshiko, Milaneschi, Yuri, Zhang, Yongqing, Becker, Kevin G., Zukley, Linda, Ferrucci, Luigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546625/
https://www.ncbi.nlm.nih.gov/pubmed/28786993
http://dx.doi.org/10.1371/journal.pone.0181100
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author Tanaka, Toshiko
Milaneschi, Yuri
Zhang, Yongqing
Becker, Kevin G.
Zukley, Linda
Ferrucci, Luigi
author_facet Tanaka, Toshiko
Milaneschi, Yuri
Zhang, Yongqing
Becker, Kevin G.
Zukley, Linda
Ferrucci, Luigi
author_sort Tanaka, Toshiko
collection PubMed
description 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
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spelling pubmed-55466252017-08-12 A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study Tanaka, Toshiko Milaneschi, Yuri Zhang, Yongqing Becker, Kevin G. Zukley, Linda Ferrucci, Luigi PLoS One Research Article 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 Public Library of Science 2017-08-07 /pmc/articles/PMC5546625/ /pubmed/28786993 http://dx.doi.org/10.1371/journal.pone.0181100 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Tanaka, Toshiko
Milaneschi, Yuri
Zhang, Yongqing
Becker, Kevin G.
Zukley, Linda
Ferrucci, Luigi
A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study
title A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study
title_full A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study
title_fullStr A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study
title_full_unstemmed A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study
title_short A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study
title_sort double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: a pilot study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546625/
https://www.ncbi.nlm.nih.gov/pubmed/28786993
http://dx.doi.org/10.1371/journal.pone.0181100
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