the activity of IL-18. Moreover, IL-37 binds to single immunoglobulin IL-1 receptor related protein (SIGIRR), also known as IL-1R8 or TIR8, which forms a complex with IL-18R? and induces an anti-inflammatory response. The IL-37/IL-18R?/IL-1R8 complex activates the STAT3 signaling pathway, decreases NF-?B and AP-1 activation and reduces IFN?