It is believed that TNF and IL-6 are critical pro-inflammatory cytokines that promote osteoclast maturation leading to cartilage degeneration and matrix degradation, and can induce the release of other stimulating factors (such as IL-1), resulting in a vicious cycle of unrelieved synovitis in RA (Bertolini et al., 1986; Ohshima et al., 1998). Here, TNF is linked to rheumatoid arthritis.