TNF and rheumatoid arthritis: M1 macrophages produce large amounts of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), which intensify inflammation and cause tissue damage, playing a key role in chronic inflammation in RA, where their release of inflammatory cytokines leads to joint damage and disease worsening (42).