Tumor necrosis factor-alpha

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

Cachectin; TNF; TNF-alpha; TNFSF2; TNFα; TNF-α; Tumor Necrosis Factor; Tumor necrosis factor alpha; Tumor necrosis factor ligand superfamily member 2; Tumor Necrosis Factor-α

Definition
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Multifunctional proinflammatory cytokine involved in a central function in local and systemic inflammation. TNF-alpha is one of the best-studied representatives of the so-called TNF/TNFR superfamily, a cytokine system that plays a central role in the immune response and organogenesis, especially of the lymphatic system. It plays a central role in the pathogenesis of psoriasis and other inflammatory processes (Crohn's disease, arthritis; pathogenesis of contact allergy). It causes haemorrhagic necrosis in certain tumours.

General information
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TNF-α exists biologically in soluble or transmembrane form. TNF-α molecules interact with at least 2 receptors (TNFRc-1 or TNFRc-2). The interaction of TNF-α with its receptors (especially TNFRc-1) activates signalling cascades which can lead to apoptosis (via caspase-8; see below caspases) and cell activation (via NF-κB) (see below transcription factors). The balance of antagonistic effects of both signal inductions depends on the cellular environment in which the stimulation by TNF-α takes place. Relevant for inflammation is the NF-κB mediated reaction, in the course of which pro-inflammatory enzymes such as interleukins (especially IL-6 and IL-8) are released.

Occurrence
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TNF-α is mainly produced and released by macrophages, but also by a large number of other cells such as lymphocytes, mast cells, endothelial cells, heart muscle cells, fibroblasts and neuronal tissue. Large amounts of TNF-α are released in response to bacterial products (e.g. lipopolysaccharides) and interleukin-1β. Formation is stimulated by Toll-like receptors and the MAP signalling pathway as well as NF-kappaB. It also has effects on lipid metabolism, blood clotting, insulin resistance and various endothelial functions.

Therapy
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TNF-α and its interactions with its receptors are pharmacologically important targets of various drugs. Drug classes which are effective in biological immunotherapy of various diseases, including Crohn's disease, rheumatoid arthritis and psoriasis. S.a. Infliximab, Etanercept, Golimumab.

Note(s)
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TNF-α was already described in 1975 as a factor that led to tumor regression in bacterial diseases.

Literature
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  1. Alexis A et al (2005) Off-label dermatologic uses of anti-TNF-a therapies. J Cutan Med Surg 9: 296-302
  2. Wakefield PE, James WD et al (1991) Tumor necrosis factor. J Am Acad Dermatol 24: 675-685
  3. Carter PH et al (2001) Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-α. PNAS 98: 11879-11884
  4. Hehlgans, T et al (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 115: 1-20
  5. Seneschal J et al (2007) Psoriasiform drug eruptions under anti-TNF treatment of arthritis are not true psoriasis. Acta Derm Venereol 87: 77-80
  6. Tracey KJ (2002) The inflammatory reflex. Nature 420: 853-859

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Last updated on: 29.10.2020