Systemic and liver cytokine activation. Implications for liver regeneration and posthepatectomy endotoxemia and sepsis.
BACKGROUND
The liver is known to be an important site of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) production during infection, but local changes in these cytokines after liver resection are unknown.


METHODS
Fischer rats were subjected to 70% hepatectomy or sham operation to determine if hepatic resection alters liver cytokine production and subsequent response to infection.


RESULTS
During liver regeneration, circulating IL-6 levels were mildly increased but no expression of TNF-alpha or IL-6 could be detected in the regenerating livers. However, the capacity for the regenerating liver to produce cytokines was intact, since intraperitoneal Escherichia coli endotoxin (2 mg/kg) produced liver cytokine messenger RNA levels in hepatectomized animals comparable to those in pair-fed controls. Systemic response to endotoxin and sepsis was also intact after hepatectomy, as circulating cytokine response was similar between hepatectomized and pair-fed animals after endotoxin administration as well as after cecal ligation and puncture.


CONCLUSIONS
Hepatectomy elicits a circulating cytokine response without effects on liver IL-6 or TNF-alpha production. However, cytokine defense mechanisms are intact during noncomplicated liver regeneration, as indicated by normal TNF-alpha and IL-6 responses to endotoxemia or sepsis. Endotoxemia is a more potent stimulus for liver cytokine production than local trauma or liver regeneration, suggesting that not only the proximity to injury but also the severity and mechanisms of injury determine local cytokine responses.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
P
P
Enayati
M F
MF
Brennan
Y
Y
Fong
D000818:Animals; D001483:Base Sequence; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli; D006498:Hepatectomy / Q000009:adverse effects*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008099:Liver / Q000276:immunology*; D008115:Liver Regeneration / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011916:Rats, Inbred F344; D018805:Sepsis / Q000276:immunology; D014115:Toxemia / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha