During this process, a variety of both inflammatory and noninflammatory mediators, including proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), the metalloproteinases (MMPs), CD4+ cells, B lymphocytes, macrophages and synovial fibroblasts, contribute to the pathogenesis of RA. This evidence concerns the gene IL1B and rheumatoid arthritis.