TNF and arthritic joint disease: TNF-α and IL-1β are the two primary cytokines involved in the initiation and progression of arthritis [42], mainly through (a) downregulation of the synthesis of major extracellular matrix components by inhibiting anabolic activities of chondrocytes [43,44]; (b) induction of additional cytokines (such as IL-6), chemokines, and extra cellular matrix degrading enzymes (MMPs and aggrecanases) [45,46]; (c) inhibition of anti-oxidant activity of the host [47]; and (d) induction of reactive oxygen species [48].