TNF and rheumatoid arthritis: The various signaling mechanisms involved in the pathogenesis of RA, including Toll-like receptors (TLRs) of the innate immune system, apoptosis-encouraging effector molecules, intracellular kinases, signaling pathways, and proinflammatory cytokine facilitators such as interleukins (IL-6, IL-1β), tumor necrosis factor-alpha (TNF-α), and C-reactive proteins, are all important.