The role of the four 'classical' IL-1 family members (for instance, IL-1α, IL-1β, IL-1Ra and IL-18) in the pathogenesis and development of RA was illustrated in mouse models of arthritis, particularly by the spontaneous arthritis that develops in IL-1α transgenic mice [18] as well as in IL-1Ra deficient mice [19]. This evidence concerns the gene IL18 and arthritic joint disease.