Tumor necrosis factor-alpha
Introduction
Tumor necrosis factor-alpha (TNF-α) is a cell-signaling protein involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. It is produced chiefly by activated macrophages, although it can be produced by other cell types as well.
Structure
TNF-α is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain. The protein is initially produced as a type II transmembrane protein, which is cleaved by the enzyme TNF alpha converting enzyme (TACE) to produce a soluble form of the protein.
Function
TNF-α is a proinflammatory cytokine that can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. It has the ability to induce fever, apoptotic cell death, inflammation, inhibit tumorigenesis and viral replication, and respond to sepsis via IL1 & IL6 producing cells.
Role in Disease
TNF-α has been implicated in a variety of diseases including Alzheimer's disease, cancer, major depression, psoriasis and inflammatory bowel disease (IBD). Although controversial, studies are ongoing to determine whether TNF-α blockade can help with these conditions.
Clinical Use
Drugs that block the action of TNF-α have been used to treat diseases such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. These drugs include infliximab, etanercept, and adalimumab.