Vol.20 No.3

Review Article

Cryopyrin-associated periodic syndromes: background and therapeutics

Authors

Tetsuo Kubota1 , Ryuji Koike2

  • Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
  • Clinical Research Center, Tokyo Medical and Dental University, Tokyo, Japan
Received:

6 August 2009

Accepted:

22 December 2009

Published online:

6 February 2010

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Abstract

Cryopyrin-associated periodic syndromes (CAPS) are caused by mutations of the gene encoding the NLR family protein NLRP3, which together with caspase-1 and adaptor proteins constitutes a protein complex termed the inflammasome. In innate immune reactions, a variety of stimuli activate the NLRP3 inflammasome, triggering caspase-1 to process proIL-1 and thus to produce mature IL-1. Excessive production of IL-1 by monocytes/macrophages is the central pathophysiology of CAPS, and daily injection of the IL-1 receptor antagonist anakinra rapidly ameliorates the inflammatory symptoms in most cases. Furthermore, double-blind, placebo-controlled clinical trials have recently confirmed the efficacy and safety of rilonacept, a fusion protein of the IL-1 receptor and IgG Fc, and canakinumab, a human anti-IL-1 monoclonal antibody, as novel long-lasting agents for treating CAPS.

Key words

Autoinflammatory diseases - Cryopyrin-associated periodic syndromes - Inflammasome - NLRP3 - IL-1 blockade