How to modulate inflammatory cytokines in liver diseases.
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-alpha (TNF-alpha)-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-alpha neutralization is not harmful to patients chronically infected with this virus. In contrast, neutralization of TNF-alpha 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.
Tilg
Herbert
H
Department of Medicine, Division of Gastroenterology and Hepatology, Innsbruck Medical University, Austria. Herbert.Tilg@uibk.ac.at
Kaser
Arthur
A
Moschen
Alexander R
AR
D052242:Adiponectin / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000627:therapeutic use; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10