TNF and rheumatoid arthritis: TNF-α is clearly a central cytokine in RA pathophysiology, which has a pivotal role in the initiation and amplification of the cytokine cascade (41–45), and mediate a wide variety of effector functions relevant to the pathogenesis of RA, including leukocyte and endothelial activation, synoviocyte activation and survival, cytokine and chemokine amplification, angiogenesis, and nociceptor activation (46, 47).