Cytokine regulation of liver injury and repair.

Journal Article (Journal Article;Review)

By comparing the hepatic responses to tumor necrosis factor (TNF)-alpha that occur during situations that promote liver injury (such as obesity or chronic exposure to ethanol) with those that occur after stimuli (such as partial hepatectomy) that lead to liver regeneration, it is apparent that hepatocytes are usually able to constrain noxious responses to TNF-alpha, such as the release of reactive oxygen from mitochondria. It appears that by promptly upregulating survival genes that regulate mitochondrial membrane permeability, hepatocytes are usually able to constrain noxious responses, including the release of mitochondrial-generated reactive oxygen species, that follow exposure to potentially toxic cytokines, such as TNF-alpha. Indeed, transient TNF-alpha-mediated increases in ROS may even be exploited by hepatocytes to evoke a subsequent proliferative response. Thus, the healthy liver has well-developed defense mechanisms that permit hepatocytes to adapt to cytokine-initiated stress, protecting them from cytokine-mediated lethality. Nevertheless, these same cytokines may cause liver injury when hepatocytes have been pre-exposed to toxins (e.g. ethanol) that interfere with their usual protective responses. Furthermore, while transient adaptations to cytokine-initiated stress permit hepatocytes to survive and proliferate, persistence of these anti-apoptotic, adaptative responses (as occurs, for example, in fatty livers) may inadvertently enhance hepatocyte vulnerability to necrosis when the liver is confronted by secondary insults that promote mitochondrial membrane depolarization.

Full Text

Duke Authors

Cited Authors

  • Diehl, AM

Published Date

  • April 2000

Published In

Volume / Issue

  • 174 /

Start / End Page

  • 160 - 171

PubMed ID

  • 10807515

International Standard Serial Number (ISSN)

  • 0105-2896

Digital Object Identifier (DOI)

  • 10.1034/j.1600-0528.2002.017411.x


  • eng

Conference Location

  • England