TNF and rheumatoid arthritis: In active disease, pro-inflammatory MDMs constitute the majority of synovial macrophages (49), and when isolated from inflamed tissues of RA patients with active disease release proinflammatory mediators (such as TNF, IL-1, IL-6, CXCL8 and CCL2) (57–59) and were able to stimulate autologous T cells (60).