TNF and rheumatoid arthritis: However, the activation of multiple downstream signal transduction pathways by NO, IFN-γ, MRP-8/14, and other proinflammatory cytokines, namely, tumor necrosis factor-α (TNF-α), IL-6, IL-8, IL-12/23, IL-18, and so forth [13] has profound implications for any future therapeutic interventions for RA [14–17] because it would be unlikely that suppression or inhibition of any one of these signaling pathways would ameliorate the inflammation of RA or reduce articular cartilage destruction and/or subchondral bone erosions characteristic of RA [18].