Journal
JOINT BONE SPINE
Volume 74, Issue 6, Pages 571-576Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.jbspin.2007.04.004
Keywords
IL-1 beta; monosodium urate; periodic fever; inflammasome; NALP3
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IL-1 beta is a cytokine with major roles in inflammation and innate immune responses. IL-1 beta is produced as an inactive proform that must be cleaved within the cell to generate biologically active IL-1 beta. The enzyme caspase-1 catalyzes the reaction. Recent work showed that caspase-1 must be activated by a complex known as the inflammasome. The inflammasome comprises NALP, which is an intracellular receptor involved in innate immunity, and an ASC adapter that ensures caspase-1 recruitment to the receptor. The most extensively described inflammasome to date is formed by the NALP3 receptor within monocytes. Mutations involving the NALP3 gene cause hereditary periodic fever syndromes in humans. Increased inflammasome activity responsible for uncontrolled IL-1 beta production occurs in these syndromes. Inhibition of the IL-1 beta pathway by IL-1 receptor antagonist (anakinra) is a highly effective treatment for inherited periodic fever syndromes. A major role for inflammasome activity in the development of gout attacks was established recently. Urate monosodium crystals are specifically detected via the NALP3 inflammasome, which results in marked IL-1 beta overproduction and initiation of an inflammatory response. This finding opens up new possibilities for the management of gouty attacks. (C) 2007 Elsevier Masson SAS. All rights reserved.
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