Study confirms protein culprit in alcohol-induced liv...( UNC-CH School of Medicine Chapel Hil...)

UNC-CH School of Medicine, Chapel Hill-- For the first time, scientists at the University of North Carolina at Chapel Hill have used gene knockout technology to firmly identify a key molecular player in alcohol-induced liver disease . A report of the study appears October 1 in the journal Gastroenterology. The findings carry implications for targeting new treatments aimed at preventing alcohol-induced hepatitis and cirrhosis.

"Having this knock-out technology will help us develop drug therapies for this devastating disease which affects 11 million people in the United States alone," says senior study author Dr. Ronald G. Thurman, professor of pharmacology at UNC-CH School of Medicine.

The report points to tumor necrosis factor-alpha (TNF-alpha) as the liver injury culprit. This hormone-like protein is produced in the liver and cells throughout the body. An immune system cytokine, it is a central pro-inflammatory molecule.

The study offers the first solid proof that TNF-alpha figures importantly in the development of early liver injury associated with long-term alcohol consumption. Previously, higher levels of TNF-alpha were found in alcoholics with hepatitis and laboratory studies have shown that antibodies to TNF-alpha attenuated alcohol-induced liver injury. But the cytokine's role in the disease remained unclear.

"This major increase in our understanding of mechanisms of liver injury brings us one step closer to therapies for alcoholic liver disease," says Dr. Enoch Gordis, director, National Institute on Alcohol Abuse and Alcoholism, a component of the National Institutes of Health.

Thurman explains the production of TNF-alpha in the liver occurs in phagocytes called Kupffer cells. These white cells help kill bacteria , including endotoxin - pieces of raw, gram-negative bacteria that get into the liver via the intestines. Studies suggest that alcohol intake increases the gut's permeability, thus releasing increas
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Contact: Lynn Wooten
Lwooten@unch.unc.edu
919-966-6046
University of North Carolina School of Medicine
1-Oct-1999