How to modulate inflammatory cytokines in liver diseases


Herbert Tilg, MD, Department of Medicine, Division of Gastroenterology and Hepatology, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Tel: 43-512-504-23251
Fax: 43-512-504-23391


Abstract: Most acute and chronic liver diseases are characterized by inflammatory processes with enhanced expression of various pro- and anti-inflammatory cytokines in the liver. These cytokines are the driving force of many inflammatory liver disorders often resulting in fibrosis and cirrhosis.

Severe alcoholic hepatitis is a prototypic tumor necrosis factor-α (TNF-α)-associated disease. This knowledge has recently led to pilot studies with promising results investigating specific anti-TNF drugs such as infliximab or etanercept in the treatment of this disease, although a recently performed controlled French study did show a potential detrimental effect of this approach. Anti-TNF treatment strategies might also improve chronic hepatitis C infection as shown by one controlled trial using etanercept administered subcutaneously for 24 weeks. Furthermore, several case reports suggest that TNF-α neutralization is not harmful to patients chronically infected with this virus. In contrast, neutralization of TNF-α worsens and might even be associated with fatalities in chronic hepatitis B infection. Anti-inflammatory cytokines such as interleukin-10 (IL-10) have also been tried in patients with chronic liver diseases. Whereas IL-10 administered to patients with chronic hepatitis C virus infection shows indeed anti-inflammatory effects in the liver, it seems to act as a proviral agent thereby limiting its clinical utility. Another cytokine with major anti-inflammatory potential is the adipokine adiponectin, as its administration is beneficial in many experimental models of liver injury. Interference with cytokine pathways and/or administration of anti-inflammatory cytokines will be of major interest in the future therapy of many liver diseases.