Tumor necrosis factor (TNF) (TNF)

Tumor necrosis factor (TNF) is a pleiotropic pro-inflammatory cytokine primarily secreted by macrophages and T-cells that plays a central role in the regulation of immune cells and systemic inflammation (UniProt: P01375). It exists in both transmembrane and soluble forms, signaling through two distinct receptors, TNFR1 and TNFR2, to activate pathways such as NF-κB and MAP kinase, which mediate cell survival, proliferation, or apoptosis (PubMed: 28524695). Dysregulation of TNF production is implicated in a wide range of autoimmune and inflammatory disorders, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease (StatPearls: TNF Inhibitors). Therapeutic targeting of TNF with monoclonal antibodies or soluble receptor fusion proteins has revolutionized the treatment of these chronic inflammatory conditions by neutralizing its biological activity (NIH: PMC3526509). However, TNF inhibition carries risks, including increased susceptibility to opportunistic infections like tuberculosis and potential malignancy, necessitating careful patient screening and monitoring (FDA: Boxed Warning).

Other names

TNF-alphaTumor necrosis factor-alphaCachectinTNFSF2Tumor necrosis factor ligand superfamily member 2

TNF inhibitors bind to the soluble and transmembrane forms of the TNF-alpha cytokine, preventing its interaction with the TNFR1 and TNFR2 receptors. This blockade inhibits the activation of pro-inflammatory signaling cascades, such as the NF-κB and MAPK pathways, thereby reducing the production of inflammatory mediators and the recruitment of immune cells to sites of inflammation (PubMed: 28524695, StatPearls: TNF Inhibitors).