In contrast, interleukin 1 (IL-1) receptor antagonist protein (IRAP) knock-out mice develop spontaneous arthritis due to increased production of proinflammatory cytokines (IL-1β, IL-6, IL-17, and tumour necrosis factor-alpha, TNFα) and autoantibodies in the absence of negative regulation of IL-1 signalling [41, 42]. This evidence concerns the gene IL1B and Arthritis.