Editing Tumor necrosis factor (section)

{{Short description|Immune system messenger protein which induces inflammation}}
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{{Distinguish|lymphotoxin alpha}}
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'''Tumor necrosis factor''' ('''TNF'''), formerly known as '''TNF-α''', is a chemical messenger produced by the [[immune system]] that induces inflammation.<ref name="Microbiology(Kaiser)"/> TNF is produced primarily by activated [[macrophages]], and induces inflammation by binding to its receptors on other cells.<ref name="DeathByInflammation"/> It is a member of the [[tumor necrosis factor superfamily]], a family of [[Transmembrane protein|transmembrane proteins]] that are [[Cytokine|cytokines]], chemical messengers of the immune system.<ref name="pmid28275260">{{cite journal | vauthors = Croft M, Siegel RM | title = Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases | journal =  Nature Reviews Rheumatology| volume = 13 | issue = 4 | pages = 217–233 | date = March 2017 | pmid = 28275260 | pmc = 5486401 | doi = 10.1038/nrrheum.2017.22 | doi-access = free }}</ref>  Excessive production of TNF plays a critical role in several inflammatory diseases, and [[TNF inhibitors|TNF-blocking drugs]] are often employed to treat these diseases.<ref name="pmid=33800290"/>

TNF is produced primarily by macrophages but is also produced in several other cell types, such as [[T cells]], [[B cells]], [[dendritic cells]], and [[mast cells]]. It is produced rapidly in response to pathogens, cytokines, and environmental stressors.<ref name="TNFPathophysiology"/> TNF is initially produced as a type II transmembrane protein (tmTNF), which is then cleaved by [[ADAM17|TNF alpha converting enzyme]] (TACE) into a soluble form (sTNF) and secreted from the cell.<ref name="pmid20194223"/> Three TNF molecules assemble together to form an active [[homotrimer]], whereas individual TNF molecules are inert.<ref name="pmid20194223"/>

When TNF binds to its receptors, [[tumor necrosis factor receptor 1]] (TNFR1) and [[tumor necrosis factor receptor 2]] (TNFR2), a pathway of signals is triggered within the target cell, resulting in an inflammatory response. sTNF can only activate TNFR1, whereas tmTNF can activate both TNFR1 and TNFR2,<ref name="DeathByInflammation"/> as well as trigger  inflammatory signaling pathways within its own cell.<ref name="tmTNFReverseSignaling"/> TNF's effects on the immune system include the activation of white blood cells, [[blood coagulation]], secretion of cytokines, and [[fever]].<ref name="Microbiology(Kaiser)"/> TNF also contributes to [[homeostasis]] in the [[central nervous system]].<ref name="TNFOnCNS"/>

Inflammatory diseases such as [[rheumatoid arthritis]], [[psoriasis]], and [[inflammatory bowel disease]] can be effectively treated by drugs that inhibit TNF from binding to its receptors.<ref name="pmid=33800290"/> TNF is also implicated in the pathology of other diseases including [[cancer]], [[liver fibrosis]], and [[Alzheimer's]], although TNF inhibition has yet to show definitive benefits.<ref name="MetabolicMessengers">{{cite journal | vauthors = Sethi JK, Hotamisligil GS | title = Metabolic Messengers: tumour necrosis factor | journal =  Nature Metabolism| date = October 2021 | volume = 3 | issue = 10 | pages = 1302–1312 | doi = 10.1038/s42255-021-00470-z | doi-access = free | pmid = 34650277 }}</ref>