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Free circulating interleukin-18 is increased in Schnitzler syndrome: a new autoinflammatory disease?

Abstract
Schnitzler syndrome is a rare disease characterised by chronic urticaria and arthralgia. The recent evidence that the IL-1 receptor antagonist IL-1Ra could induce rapid and complete remission of Schnitzler symptoms has pointed to IL-1 as a major pathological factor in this disease. To examine the possibility that Schnitzler syndrome may be considered to be an autoinflammatory disease, in this study we measured the serum levels of IL-18, another cytokine of the IL-1 family that is cleaved by caspase-1, in two recently diagnosed Schnitzler patients before and after treatment with IL-1Ra. In parallel, mRNA expression of IL-1 family cytokines and caspase-1 were assessed in isolated blood monocytes. Treatment with IL-1Ra significantly inhibited IL-1beta gene expression, indicating that IL-1beta activity in Schnitzler syndrome is central to IL-1beta gene upregulation in a type of auto-amplification loop. While no IL-1beta was detected in serum, free circulating IL-18 was increased in patients with Schnitzler syndrome, despite low IL-18 gene expression in monocytes. This suggests constitutive activation of the IL-1beta/IL-18-producing inflammasome, and supports the hypothesis that Schnitzler's syndrome is a new autoinflammatory disease.
AuthorsPaola Migliorini, Isabella Del Corso, Cristina Tommasi, Diana Boraschi
JournalEuropean cytokine network (Eur Cytokine Netw) Vol. 20 Issue 3 Pg. 108-11 (Sep 2009) ISSN: 1952-4005 [Electronic] France
PMID19825519 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-18
  • interleukin-18 binding protein
Topics
  • Aged
  • Gene Expression Regulation
  • Humans
  • Inflammation (blood, complications, immunology)
  • Intercellular Signaling Peptides and Proteins (blood)
  • Interleukin-18 (blood, genetics)
  • Male
  • Middle Aged
  • Schnitzler Syndrome (blood, complications, immunology)

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