The major pro-inflammatory cytokines in RA, TNF-α, IL-6, and IL-1 induced STAT3 activation either directly or indirectly and stimulated expression of IL-6 family cytokines and receptor activator of nuclear factor kappa B ligand (RANKL) in an autocrine/paracrine manner in vivo and in vitro. The gene discussed is TNF; the disease is rheumatoid arthritis.