Macrophages are key effectors in RA pathogenesis through the production of proinflammatory cytokines such as TNF-α, IL-1, IL-6, IL-8 and granulocyte macrophage colony-stimulating factor (GM-CSF) [38-40] that stimulate cells in the local microenvironment, including fibroblasts and osteoclasts, as well as in distant sites in the body. This evidence concerns the gene TNF and rheumatoid arthritis.