Kinetics of intrahepatic pro-inflammatory and anti-inflammatory responses and their relation to endotoxin-induced hepatic damage

Objective To investigate change rules and roles of intrahepatic pro-inflammatory and anti-inflammatory responses to provide experimental evidence for further elucidation of the pathogenesis of endotoxin-induced hepatic damage. Methods Mouse model of endotoxemia or endotoxin shock was produced by injection of different doses of lipopolysaccharide (LPS, E. coli O26:B6) via tail vein. The levels of TNFa, IL-6, IL-4 and IL-10 in liver tissue were assayed with ELISA. Results The levels of TNFa and IL-6 in liver tissue in both low- and high-dose groups were shown to be increased 1 hour after the injection of LPS. IL-6 level in both groups peaked at the 3rd hour and was significantly higher than that in the control group at the 8th hour. The levels of TNFa and IL-6 in liver tissue were markedly higher in high-dose group than in low-dose group. The levels of IL-4 and IL-10 in liver tissue in both groups, though being not significantly changed 1 hour after the injection of LPS, were significantly increased at the 3rd hour and still markedly higher at the 8th hour. The levels of IL-4 and IL-10 in liver tissue in high-dose group were significantly higher than those in low-dose group. The changes in intrahepatic pro-inflammatory and anti-inflammatory cytokines were shown to be paralleled to hepatic structural damage and dysfunction. Conclusions Pro-inflammatory and anti-inflammatory responses successively occurred during endotoxin-induced hepatic damage. The imbalance between their reaction may be the important mechanism for endotoxin-induced hepatic damage. Therefore, the synthetic action of local pro-inflammatory and anti-inflammatory responses should be taken into account in the treatment of endotoxin-induced hepatic disease.