Cytokines and soluble receptors of the IL-1 family in Schnitzler syndrome.

Objectives: Schnitzler syndrome (SchS) is an autoinflammatory disorder characterized by chronic urticaria, fever, monoclonal gammopathy. The success of IL-1 blocking therapies suggests a crucial role of IL-1 in disease induction. The aim of this study is to perform a comprehensive analysis of IL-1 family cytokines and soluble receptors in a group of SchS patients. Methods: Three patients fulfilling the criteria for the diagnosis of SchS were recruited; 86 blood donors formed the control group. IL-1 family cytokines (IL-1?, IL-1?, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, sIL-1R4) and antagonists (IL-1Ra, IL-18 binding protein -IL-18BP) were measured by a multiarray ELISA assay. Free IL-18 was calculated as the amount of IL-18 not inhibited by IL-18BP. Cytokine levels were compared by Mann Whitney test. Results: IL-18 and free IL-18 were increased in patients vs. controls (p=0.005 and p=0.0082, respectively), while IL-18BP levels were not different. IL-1?, IL-1? and IL-33 were undetectable in both patients and controls. The soluble receptors sIL-1R1, sIL-1R2 and ST2/sIL-1R4, and the IL-1 antagonist IL-1Ra were all within the normal range; sIL-1R3 levels were significantly lower in patients vs. controls (p= 0.039). Conclusions: The data indicate that SchS is characterized by increased circulating levels of free IL-18, possibly leading to a higher activation of innate/inflammatory effector cells. At variance with other inflammatory diseases, the lack of increase in sIL-1R1 and sIL-1R2 and the decreased levels of sIL-R3 imply a failure in the counterbalancing mechanism aimed at inhibiting excessive IL-1? in the tissues.