Effect of TNF gene depletion on liver regeneration after partial hepatectomy in mice.
BACKGROUND
Tumor necrosis factor-alpha (TNF) is thought to act as a stimulator for initiating hepatocyte proliferation after partial hepatectomy (PH). At the same time, TNF induces a series of inflammatory responses that may be detrimental for the liver and other remote organs. The purpose of this study was to investigate the effect of TNF on the pathophysiologic state after PH.


METHODS
Wild-type (TNF+/+) and TNF-deficient (TNF-/-) mice underwent 70% PH. Hepatocyte proliferation was assessed by bromodeoxyuridine labeling and mitotic index. Liver function was evaluated by alanine aminotransferase (ALT) and total bilirubin levels in serum after PH. Myeloperoxidase activity in the liver and lung was measured as a marker for neutrophil activation.


RESULTS
No differences were observed in liver regeneration or hepatocyte proliferation between TNF+/+ and TNF-/- mice. The survival of TNF-/- mice on day 1 after PH was significantly higher than that of TNF+/+ mice, but both groups had similar survival thereafter. The ALT level was significantly higher in TNF+/+ mice 6 hours after PH and myeloperoxidase activities in both liver and lung were markedly elevated in TNF+/+ mice compared with TNF-/- mice.


CONCLUSIONS
These findings demonstrate that TNF gene-depleted mice do not demonstrate delayed liver regeneration but do suppress neutrophil activation after PH compared with results in wild-type (TNF +/+) mice.
Fujita
J
J
Department of Surgery, New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, NY 10021, USA.
Marino
M W
MW
Wada
H
H
Jungbluth
A A
AA
Mackrell
P J
PJ
Rivadeneira
D E
DE
Stapleton
P P
PP
Daly
J M
JM
D000818:Animals; D002455:Cell Division; D005260:Female; D017353:Gene Deletion; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000201:enzymology; D008115:Liver Regeneration / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase