Home > Tumor necrosis factor
In medicine, tumor necrosis factor alpha (TNFα, cachexin or cachectin) is an important cytokine involved in systemic inflammation and the acute phase response.1 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.
2 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 endotoxinEndotoxin is part of the outer membrane of the cell wall of Gram-negative bacteria. It refers to the lipopolysaccharide (LPS) complex associated with the outer membrane of Gram-negative bacteria. LPS is also called endotoxin owing to its historical discov. It has a number of actions on various organ systems, generally together with interleukins 1 and 6:
- On the hypothalamusIn the anatomy of mammals, the hypothalamus is a region of the brain located below the thalamus, forming the major portion of the ventral region of the diencephalon and functioning to regulate certain metabolic processes and other autonomic activities.:
- Stimulating of the hypothalamic-pituitary-adrenal axisThe hypothalamic-pituitary-adrenal axis HPA axis is a major part of the neuroendocrine system that controls reactions to stress. Species from humans to the most ancient organisms share components of the HPA axis. It is the mechanism for a set of interacti by stimulating the release of corticotropin releasing hormone (CRH).
- Suppressing appetiteThe appetite is the desire to eat food, felt as hunger. It exists in all higher lifeforms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the (hence its name "cachexin" - cachexiaCachexia is loss of weight, muscle wasting, fatigue, weakness and decrease of appetite in someone who is not actively trying to lose weight. It can be a sign of various underlying disorders; when a patient presents with cachexia, a doctor with generally c is severe weight loss in illnessIllness can be a synonym for disease or it can be a person's perception of having poor health. Disease is an actual physical, pathophysiological process which can cause an abnormal condition of the body or mind. See disease for more information. Illness a).
- 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.
3 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 and psoriasis.
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.
