Systemic and liver cytokine activation. Implications for liver regeneration and posthepatectomy endotoxemia and sepsis
P. Enayati, M. F. Brennan and Y. Fong
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
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. DESIGN: 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. CONCLUSION: 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.
