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Review
.2012 May 31:142:w13590.
doi: 10.4414/smw.2012.13590. eCollection 2012.

Interleukin-1, inflammasomes, autoinflammation and the skin

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Free article
Review

Interleukin-1, inflammasomes, autoinflammation and the skin

Emmanuel Contassot et al. Swiss Med Wkly..
Free article

Abstract

Interleukin 1, one of the first cytokines discovered in the 1980s, and a potent mediator of fever, pain and inflammation, is at present experiencing a revival in biology and medicine. Whereas the mechanism of activation and secretion of interleukin 1β, which critically regulates the function of this molecule, has remained mysterious for some 30 years following its discovery, the identification of a new cytoplasmic complex of proteins regulating IL-1β activation and secretion has carried our understanding of the role of IL1 in biology and disease one big step further. The inflammasomes, recently identified innate immune complexes that sense intracellular danger- (e.g. uric acid, ATP, cytoplasmic DNA) or pathogen-associated molecular patterns (e.g. muramyl dipeptide, flagellin, anthrax lethal toxin), are now known to be responsible for triggering inflammation in response to several molecular patterns, including, for example, uric acid, a danger-associated molecular pattern and trigger of gout. Dysregulation of inflammasome function is however also the cause of a family of genetic autoinflammatory diseases known as cryopyrin-associated periodic syndromes (CAPS) characterised by recurrent episodes of fever, urticarial-like skin lesions, systemic inflammation and arthritis. In mouse models recapitulating mutations observed in CAPS, neutrophilic inflammation of the skin is a cardinal feature, in a manner similar to several autoinflammatory diseases with skin involvement such as PAPA (pyoderma gangrenosum, acne and pyogenic arthritis) and Schnitzler's syndrome, in which IL-1β very probably plays a pathogenic role. In this article the role of the inflammasome in IL-1 biology, autoinflammation and disease is reviewed, together with new avenues for the therapy of these diseases.

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