COMMONLY used gout medications could offer protection from alcohol-induced liver disease and inflammation, according to the results of new research in mice. These findings indicate that clinical trials in humans with alcoholic liver disease could be a prudent next step.
“This study should ultimately help patients with alcoholic liver disease to prevent and/or treat acute episodes of alcoholic hepatitis, a potentially lethal condition,” said a co-author of the study, Dr Gyongyi Szabo, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
The discovery was based upon experiments by Dr Szabo and colleagues, which involved extraction of immune cells from human volunteers as well as from four groups of mice. In the human cell trials, immune cells were isolated and exposed to alcohol-treated human hepatocytes in a test tube. Data showed that uric acid and ATP, both of which are components released from alcohol-damaged hepatocytes, were able to activate the inflammasome, a component of the innate immune system.
In the mouse trials, the first group comprised of wild-type mice and the second had mice deficient in the NLRP3 component of the inflammasome; both groups received chronic alcohol-containing diet. The third group comprised of wild-type and the fourth NLRP3-deficient mice; both groups received control alcohol-free diet. Of the mice that were fed a chronic alcohol diet, the wild-type mice developed characteristics of alcoholic liver disease while the NLRP3-deficient mice did not develop such symptoms. The researchers also found that alcohol-induced liver damage was associated with an increase in the circulating levels of the sterile danger molecules, uric acid and ATP.
“We are increasingly appreciating the central role of inflammation and immune responses in a variety of diverse diseases,” said Dr John Wherry, Deputy Editor of the Journal of Leukocyte Biology, in which the research was first published. “The link between alcohol induced tissue damage and sensing by the immune system through the inflammasome opens the door for new therapeutics targeting this type of inflammation in liver diseases.”