ABSTRACT
Cytokines constitute a broad family of infl ammatory and regulatory mediators that play outstanding roles in organic complications of alcoholism, contributing to the protean manifestations of this disease. Alcohol increases gut permeability to endotoxin, leading to Kupff er cell activation and pro-infl ammatory cytokine secretion. Th is initiates a cascade of events characterized by infl ammation, lipid peroxidation, neutrophil recruitment, and immune activation, closing a positive feedback loop, ultimately leading to liver cell necrosis and apoptosis. Th erefore, alcoholic hepatitis can be considered as a TNF-α-mediated disease; in more advanced stages of the disease, TGF-β plays a more important role, promoting fi brosis both in the liver (leading to cirrhosis) and in the pancreas (leading to chronic pancreatitis). Increased TNF-α favours muscle atrophy, is probably involved in neurodegeneration and brain atrophy, and contributes to alcoholic cardio-myopathy and bone alterations, together with other cytokines, especially IL-6, a well-known activator of osteoclasts. Moreover, altered cytokine secretion in alcoholics may predispose them to sepsis and severe pneumonia. However, despite the proven action of TNF-α in some organs, such as the liver, anti-TNF treatment trials in alcoholic hepatitis have led to disappointing results, suggesting that vigorous research is still needed to fully elucidate the role of these infl ammatory modulators in alcohol-related organic dysfunction.
