Academic journal article Alcohol Research

Cytokines-Central Factors in Alcoholic Liver Disease

Academic journal article Alcohol Research

Cytokines-Central Factors in Alcoholic Liver Disease

Article excerpt

Many processes related to the consumption or breakdown of alcohol that contribute to alcohol-induced liver disease are mediated by small proteins known as cytokines, which are produced and secreted by liver cells and many other cells throughout the body. Through a variety of actions, cytokines regulate certain biochemical processes in the cells that produce them as well as in neighboring cells. For example, in case of an infection, they attract white blood cells to the tissues, triggering an inflammatory response. In the liver, persistent cytokine secretion resulting in chronic inflammation leads to conditions such as hepatitis, fibrosis, and cirrhosis. Cytokines also regulate a process known as programmed cell death, or apoptosis, which is in part responsible for alcohol-induced destruction of liver tissue. Two cytokines--tumor necrosis factor alpha and transforming growth factor beta--play prominent roles in apoptosis. Finally, a cytokine network mediates the harmful effects of a bacterial protein called endotoxin on the liver. Because of their diverse functions, cytokines might make attractive targets in the prevention or treatment of alcoholic liver disease, and researchers already have obtained encouraging results when testing such approaches. KEY WORDS: cytokines; alcoholic liver disorder; biological activation; alcoholic hepatitis; fibrosis; liver cirrhosis; apoptosis; tumor necrosis factor-alpha; transforming growth factors; endotoxins; Kupffer cell; hepatocyte; disease course; disease susceptibility; immune system; chronic AODE (alcohol and other drug effects)

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Long-term excessive alcohol consumption can result in a spectrum of liver abnormalities, ranging from simple fatty liver (steatosis) or fatty liver accompanied by inflammation (steatohepatitis) to scar tissue formation (fibrosis), the destruction of the normal liver structure (cirrhosis), and even liver cancer (hepatocellular carcinoma). In its mildest form, fatty liver often causes no obvious clinical symptoms and is rarely fatal. In fact, only 15 to 20 percent of chronic heavy drinkers with steatosis have clinical liver disease, suggesting that other factors both in the drinker's body (e.g., genetic influences) and in his or her environment help determine how alcoholic liver disease develops and progresses.

For liver damage to develop, numerous processes and biochemical reactions must occur in a variety of cells normally located in the liver or attracted to the liver when that organ is exposed to alcohol. This complex array of reactions is orchestrated by proteins called cytokines, which are produced and secreted by almost all cells in the body, including liver cells.

This article discusses the role of cytokines in alcoholic liver disease. A review of the general characteristics of cytokines is followed by an introduction to the process of programmed cell death, or apoptosis, which is regulated by cytokines and accounts for at least some of the liver damage found after chronic alcohol consumption. Finally, the article explores how a bacterial protein called endotoxin contributes to alcoholic liver damage by activating immune cells in the liver to release cytokines.

CYTOKINES AND THEIR ROLE IN CELL COMMUNICATION

Almost all cells in the body, including most types of liver cells, can produce and secrete cytokines. Released cytokines then interact with the cells whose functions they modify (i.e., the target cells). These target cells can be the same ones that initially produced the cytokines; this is called an autocrine effect. In addition, the cytokines can interact with neighboring cells; this is called a paracrine effect. Regardless of what the target cell of a cytokine is, the interaction occurs through a special docking molecule (i.e., a receptor) that consists of one or more proteins. This receptor has a specific three-dimensional shape, like a lock into which the cytokine "key" fits. …

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