University of Massachusetts Medical School Faculty Publications

Title

Uric acid as a danger signal in gout and its comorbidities

UMMS Affiliation

Department of Pathology

Date

1-2013

Document Type

Article

Medical Subject Headings

Biological Markers; Cardiovascular Diseases; Comorbidity; Crystallization; Diabetes Mellitus; Gout; Humans; Hypertension; Inflammation; Interleukin-1; Uric Acid

Disciplines

Heterocyclic Compounds | Musculoskeletal Diseases | Pathological Conditions, Signs and Symptoms | Rheumatology

Abstract

Uric acid is a waste product of purine catabolism. This molecule comes to clinical attention when it nucleates to form crystals of monosodium urate (MSU) in joints or other tissues, and thereby causes the inflammatory disease of gout. Patients with gout frequently suffer from a number of comorbid conditions including hypertension, diabetes mellitus and cardiovascular disease. Why MSU crystals trigger inflammation and are associated with comorbidities of gout has been unclear, but recent studies provide new insights into these issues. Rather than simply being a waste product, uric acid could serve a pathophysiological role as a local alarm signal that alerts the immune system to cell injury and helps to trigger both innate and adaptive immune responses. The inflammatory component of these immune responses is caused when urate crystals trigger both inflammasome-dependent and independent pathways to generate the proinflammatory cytokine IL-1. The resulting bioactive IL-1 stimulates the inflammation of gout and might contribute to the development of other comorbidities. Surprisingly, the same mechanisms underlie the inflammatory response to a number of irritant particles, many of which also cause disease. These new insights help to explain the pathogenesis of gout and point to potential new therapeutic targets for this and other sterile inflammatory diseases.

Rights and Permissions

Citation: Nat Rev Rheumatol. 2013 Jan;9(1):13-23. doi: 10.1038/nrrheum.2012.143. Link to article on publisher's site

Related Resources

Link to Article in PubMed