How to modulate inflammatory cytokines in liver diseases

Liver Int. 2006 Nov;26(9):1029-39. doi: 10.1111/j.1478-3231.2006.01339.x.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adiponectin / metabolism
  • Adiponectin / pharmacology
  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Cytokines / metabolism*
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Inflammation Mediators / metabolism*
  • Interleukin-10 / therapeutic use
  • Liver Diseases / drug therapy*
  • Liver Diseases / metabolism*
  • Liver Diseases / pathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Adiponectin
  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Tumor Necrosis Factor-alpha
  • Interleukin-10