Reduced liver injury in the interleukin-6 knockout mice by chronic carbon tetrachloride administration.
BACKGROUND
Interleukin-6 has been involved in restoration of liver function after partial hepatectomy and toxic liver injury. However, normal liver regeneration in interleukin-6 knockout mice has also been reported. The aim of this work was to investigate the effect of interleukin-6 deficiency on liver injury and its regeneration in a model of long term carbon tetrachloride (CCl4) administration.


METHODS
Serum and whole livers from wild type and interleukin-6 knockout mice treated with carbon tetrachloride (0.25 mL kg(-1)) twice a week were obtained after 4, 6 and 8 weeks (n = 4-6). Sections were assessed for liver regeneration, liver injury and hepatocyte apoptosis whereas sera were assayed for aminotransferase levels. Nuclear extracts and total liver lysates were assayed for transcription factor activation and apoptosis related proteins, respectively.


RESULTS
When compared to wild type, interleukin-6 knockout mice showed reduced liver damage scores, lower aminotransferase levels and diminished apoptosis, as well as reduced nuclear factor kappa B activation. Although the level of active protein was lower, activation of signal transducer and activator of transcription 3 still takes place in knockout mice. Furthermore, liver regeneration measured by bromodeoxyuridine incorporation showed no differences between wild type and knockout animals after 6 and 8 weeks of treatment.


CONCLUSIONS
Compared to the wild type mice liver regeneration after chronic treatment with carbon tetrachloride proceeds at a slower rate in interleukin-6 deficient mice. However, this low recovery rate is accompanied by a reduction not only in hepatocyte apoptosis, but also in activation of nuclear factor kappa B and liver injury.
Río
A
A
Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
Gassull
M A
MA
Aldeguer
X
X
Ojanguren
I
I
Cabré
E
E
Fernández
E
E
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000187:drug effects; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control; D008115:Liver Regeneration / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D015850:Interleukin-6; D016328:NF-kappa B; D014157:Transcription Factors; D002251:Carbon Tetrachloride