TNF and rheumatoid arthritis: M1-type macrophages are abundant in RA joints, and their activation initiates the transcription of NF-κB and hypoxia-inducible factor 1α (HIF1α), leading to the production of pro-inflammatory cytokines such as IL-1β and TNF-α and the phagocytosis of pathogens, whereas the secretion of IL-4 and IL-13 leads to alternatively activated macrophage (M2-type) formation via the activation of a Janus kinase (Jak)-3/ STAT-6 axis.