Glimmer Of Hope For Gout Patients

Main Category: Gout
Article Date: 05 Aug 2006 - 23:00 PDT

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For over 100 years we have known that the intensely painful disease gout is caused by the accumulation of monosodium urate crystals (MSU) in joints. Now, in a study appearing in the August issue of the Journal of Clinical Investigation, Kenneth Rock and colleagues from University of Massachusetts Medical School uncover how these crystal deposits are recognized by the immune system and trigger acute and painful inflammation.

Gout patients usually produce too much uric acid or are unable to efficiently excrete the uric acid excess. Rock and colleagues had previously shown that uric acid released from "damaged cells" in the body forms MSU crystals, which act as a "danger signal" that stimulates the immune response into action. The same group now shows that, in mice, MSU crystals are internalized by monocytes, resulting in the processing and maturation of the molecule pro-IL-1beta to its biologically active form IL-1beta. IL-1beta activates the IL-1beta receptor on cells around the MSU crystal-laden joints, which recruits the protein MyD88. This triggers the production of inflammatory molecules, resulting in painful joint inflammation. Surprisingly, the inflammatory reaction does not involve Toll-like receptors, which usually recognize foreign pathogens and trigger immune cell responses. In an accompanying commentary, Laurie Glimcher from Harvard Medical School comments that, "the study of the physiological function of IL-1beta in human gouty inflammation will undoubtedly provide new therapeutic tools to better manage the acute inflammation episode in patients with gout."

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Article adapted by Medical News Today from original press release.
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TITLE: MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals

AUTHOR CONTACT:
Kenneth L. Rock
University of Massachusetts Medical School, Worcester, Massachusetts, USA.
E-mail: Kenneth.rock@umassmed.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=28075

ACCOMPANYING COMMENTARY

TITLE: Gout: new insights into an old disease

AUTHOR CONTACT:
Laurie H. Glimcher
Harvard Medical School, Boston, Massachusetts, USA.
Email: lglimche@hsph.harvard.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=29404

Source: JCI table of contents: August, 2006

Contact: Brooke Grindlinger
Journal of Clinical Investigation