Tumor necrosis factor alfa
Kilde: wikipedia
In medicine, tumor necrosis factor alpha (TNFα, cachexin or cachectin) is an important cytokine involved in systemic inflammation and the acute phase response.
Structure
TNFα is a member of a group of other cytokines that all stimulate the acute phase reaction. It is a 185 amino acid glycoprotein peptide hormone, cleaved from a 212 amino acid-long propeptide. Some cells secrete shorter or longer isoforms. Genetically it links to chromosome 7p21.
Physiology
TNFα is released by white blood cells, endothelium and several other tissues in the course of damage, e.g. by infection. Its release is stimulated by several other mediators, such as interleukin 1 and bacterial endotoxin. It has a number of actions on various organ systems, generally together with interleukins 1 and 6:
- On the hypothalamus:
- Stimulating of the hypothalamic-pituitary-adrenal axis by stimulating the release of corticotropin releasing hormone (CRH).
- Suppressing appetite (hence its name "cachexin" - cachexia is severe weight loss in illness).
- Fever.
- On the liver: stimulating the acute phase response, leading to an increase in C-reactive protein and a number of other mediators.
- On other tissues: increasing insulin resistance.
Pharmacology
Inhibition of TNFα with a monoclonal antibody or a circulating receptor such as infliximab (Remicade®), etanercept (Enbrel®), or adalimumab (Humira®) are used in modern treatment of various autoimmune disorders such as rheumatoid arthritis, Crohn's disease and psoriasis. Clinical trials regarding the effectiveness of these drugs on hidradenitis suppurativa are currently ongoing. TNF or the effects of TNF are also inhibited by a number of natural compounds, including curcumin (an ingredient in turmeric) and catechins (in green tea).
Such drugs may raise the risk of contracting tuberculosis or causing a latent infection to become active. Infliximab and adalimumab have label warnings which state that patients should be evaluated for latent TB infection and treatment should be initiated prior to starting therapy with these medications.