Tumor necrosis factor (TNF-alpha)

Tumor necrosis factor (TNF-alpha) is a potent pro-inflammatory cytokine primarily produced by activated macrophages, though it is also expressed by T-cells, natural killer cells, and other tissues (UniProt P01375). It exists in two biologically active forms: a 26 kDa transmembrane protein (mTNF) and a 17 kDa soluble form (sTNF) that is released through proteolytic cleavage by the TNF-alpha converting enzyme (TACE/ADAM17) (PubMed: 23675578). TNF-alpha plays a central role in the innate and adaptive immune response by signaling through two distinct receptors, TNFR1 and TNFR2, to regulate processes such as cell proliferation, differentiation, and programmed cell death (StatPearls: TNF Inhibitors). Dysregulation and overproduction of TNF-alpha are implicated in the pathogenesis of numerous chronic inflammatory and autoimmune diseases, including rheumatoid arthritis and inflammatory bowel disease (NCBI Gene ID: 7124). Consequently, TNF-alpha has become a major therapeutic target, with several monoclonal antibodies and soluble receptor fusion proteins developed to neutralize its activity and alleviate systemic inflammation.

Other names

TNF-alphaTNFATNFSF2CachectinTumor necrosis factor ligand superfamily member 2TNF-a

Neutralization of soluble and membrane-bound TNF-alpha to prevent binding to TNF receptors (TNFR1 and TNFR2) and subsequent pro-inflammatory signaling.