WITH the help of some hard-drinking mice, researchers have shown how alcohol
abuse damages the liver. What鈥檚 more, they say a drug already on the market
could stave off such damage.
Alcohol abuse can cause inflammation of the liver, or hepatitis, which
eventually leads to scarring, or cirrhosis. Alcoholics with severe hepatitis
have higher levels of an inflammatory protein called tumour necrosis factor
alpha (TNF-&agr;) than alcoholics without liver disease. In the liver, TNF-&agr; is
mainly produced by cells called Kupffer cells, and animal experiments show that
selectively destroying these cells can prevent alcohol-induced damage.
Now a team lead by Ronald Thurman of the University of North Carolina at
Chapel Hill has found even more striking evidence that TNF-&agr; plays a central
role in alcohol-induced liver disease. The researchers genetically engineered
mice that lacked the receptor for TNF-&agr;. They gave the modified mice alcohol for
four weeks and then compared them with normal mice that drank the same amount of
alcohol.
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The mice without TNF-&agr; receptors had just a seventh as much liver damage as
the normal mice (Gastroenterology, vol 117, p 942). 鈥淲hen we took out
just one protein, we blocked almost all the injury,鈥� says Thurman. 鈥淲e didn鈥檛
expect to see so much protection.鈥� His group is now repeating the experiment
over a longer period to see if the modified mice also escape cirrhosis.
鈥淚t definitely increases our knowledge of alcohol-induced liver damage,鈥� says
Samir Zakhari of the National Institute on Alcohol Abuse and Alcoholism, near
Washington DC. He says that other factors such as the formation of free radicals
probably contribute to liver damage, but that TNF-&agr; must be a major player.
Thurman says some people with arthritis take a drug called Enbrel, which
reduces inflammation by mopping up TNF-&agr;. He hopes to test this drug in
alcoholics with hepatitis.