Prevention of carbon tetrachloride-induced rat liver injury by soluble tumor necrosis factor receptor.
OBJECTIVE
Considerable indirect evidence suggests that cytokine tumor necrosis factor alpha contributes to the hepatocellular damage caused by toxic liver injury. The effects of tumor necrosis factor alpha neutralization on liver cell injury were determined in an in vivo model of toxic liver injury.


METHODS
The in vivo effects of tumor necrosis factor alpha were examined in carbon tetrachloride liver injury through the administration of a soluble tumor necrosis factor receptor to neutralize the effects of this cytokine.


RESULTS
Soluble tumor necrosis factor receptor treatment decreased the degree of liver injury as measured by reduced levels of serum liver enzymes and improved histology. Soluble tumor necrosis factor receptor administration also lowered the mortality from a lethal dose of carbon tetrachloride from 60% to 16%. Tumor necrosis factor alpha neutralization had no detrimental effect on liver regeneration as determined by the timing of histone gene expression and postinjury liver weight.


CONCLUSIONS
These data provide direct evidence for a role of tumor necrosis factor alpha in toxin-induced liver cell injury. In addition, these investigations suggest that soluble tumor necrosis factor receptor therapy may be of benefit in the treatment of human liver disease.
Czaja
M J
MJ
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
Xu
J
J
Alt
E
E
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D006657:Histones / Q000235:genetics; D008099:Liver / Q000187:drug effects*; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D006657:Histones; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride