Intestinal barrier disfunction and endotoxemia - links in the inflammatory cascade in alcoholic liver disease

Alcoholic liver disease is a major health consequence of chronic ethanol consumption. The mechanisms by which alcohol promotes development of ALD are still not completely clear. Recent findings indicate that alcohol-related increased gut permeability may trigger the inflammatory cascade and play a crucial role in the onset and progression of this disease. Endotoxins are lipopolysaccharides (LPS) derived from the cell wall of Gram-negative bacteria. Chronic alcohol exposure may increase their penetration from the gut into the portal blood and their concentration in the liver. LPS/endotoxin recognition by Toll-like receptor 4 (TLR4) on Kupffer cells and activation of liver macrophages result in elevated synthesis of inflammatory cytokines, chemokines and reactive oxygen species (ROS). These events further account for recruitment of lymphocytes and neutrophils to the liver and promote inflammatory responses that seem to be critical in the development of alcoholic liver disease. In this review we highlight and discuss the mechanisms of alcohol- mediated alterations of intestinal barrier function as well as endothoxin-induced liver tissue injury.