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

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-1? gene expression, indicating that IL-1? activity in Schnitzler syndrome is central to IL-1? gene upregulation in a type of auto-amplification loop. While no IL-1? 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-1?/IL-18-producing inflammasome, and supports the hypothesis that Schnitzler's syndrome is a new autoinflammatory disease.