Tumour necrosis factor (TNF)

Tumour necrosis factor (TNF), formerly known as TNF-α, is a central cytokine in inflammatory reactions. TNF-neutralizing therapies have been highly successful for the treatment of chronic inflammatory and autoimmune diseases.

TNF is produced primarily by macrophages but also by other cell types, including T cells, B cells, dendritic cells, fibroblasts, mast cells, and is expressed also in the central nervous system. TNF is initially produced as a type II transmembrane protein (tmTNF), which is then cleaved by TNF alpha converting enzyme (TACE) into a soluble form (sTNF) and secreted from the cell. Three TNF molecules assemble together to form an active homotrimer. sTNF binds and activates tumour necrosis factor receptor 1 (TNFR1), and tmTNF binds and activates TNFR1 and tumour necrosis factor receptor 2 (TNFR2). When tmTNF binds to its receptors it also activates signalling pathways in its own cell. Anti-inflammatory drugs can either block TNF from binding to its receptors or block the formation of the active homotrimers. Also the naturally occurring soluble TNFRs reduce infallmatory responses. Inhibitory drugs include monoclonal antibodies infliximab, adalimumab, certolizumab pegol, and golimumab, and a circulating receptor fusion protein etanercept.

PET imaging

Etanercept has been labelled with 64Cu, and it has been used for the non-invasive investigation of TNF expression level during acute and chronic inflammation in mice (Cao et al., 2007). Certolizumab pegol has been labelled with 89Zr, and used in a transgenic rheumatoid arthritis model in mice (Beckford-Vera et al., 2020).


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Literature

Horiuchi T, Mitoma H, Harashima S, Tsukamoto H, Shimoda T. Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford) 2010; 49(7): 1215-1228. doi: 10.1093/rheumatology/keq031.

van Loo G, Bertrand MJM. Death by TNF: a road to inflammation. Nat Rev Immunol. 2023; 23(5): 289-303. doi: 10.1038/s41577-022-00792-3.



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Updated at: 2025-06-18
Created at: 2025-06-18
Written by: Vesa Oikonen