A genetic susceptible individual is exposed to one or more environmental factors, resulting in local tissue damage, autoantigen release, excessive activation of mononuclear macrophages, neutrophils and other phagocytes, and release of a large number of proinflammatory cytokines, such as IL-1, IL-6, IL-18 and proinflammatory protein S100, which eventually lead to chronic synovitis and systemic multisystem inflammation (162–165). Here, IL1B is linked to inflammation.