Glimmer Of Hope For Gout Patients
Article Date: 05 Aug 2006 - 23:00pm (PST)
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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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:
http://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:
http://https://www.the-jci.org/article.php?id=29404
Source: JCI table of contents: August, 2006
Contact: Brooke Grindlinger
Journal of Clinical
Investigation