That the altered balance between pro- and anti-inflammatory CD4+T cells and macrophages may play a key role in the cell mediated arthritogenic events concurs with clinical data showing that specific inhibitors of TNF-alpha, IL-1, and IL-6 exhibit clear-cut beneficial effects in patients with RA, and are approved as biological disease modifying antirheumatic drugs (DMARDs) for the treatment of the disease. This evidence concerns the gene TNF and rheumatoid arthritis.