Abstract:

Objective Epinephrine attenuates inflammation by inhibiting the production of pro-inflammatory cytokines, such as tumor necrosis factor(TNF)-α, interleukin (IL)-1β and by increasing the production of anti-inflammatory cytokine IL-10 in vivo and in vitro. In sepsis, activative inflammatory cells and excessive production of pro-inflammatory cytokines lead to tissue injury, multiple organ failure, and death. The liver is one of the major organ that can be damaged in sepsis and it may also trigger multiple organ dysfunction syndrome. Attenuation of hyper-inflammation may be of clinical benefit in the treatment of tissue injury associated with sepsis. So the aim of the study was to investigate the effects of epinephrine on sepsis-associated liver injury in rats. Methods Fifty SD rats were randomly divided into five groups (n=10): saline control group received intravenous 0.9% saline 2.4 mL·kg-1·h-1; LPS group received intravenous lipopolysaccharide(LPS) (Escherichia coli serotype 0111:B 4) 6 mg·kg-1); small dose epinephrine treatment group received an intravenous infusion of epinephrine 0.12μg·kg-1·min-1 after LPS intravenous injection; medium-dose epinephrine treatment group received an infusion of epinephrine 0.3μg·kg-1·min-1 after the LPS intravenous injection; large-dose epinephrine treatment group received an infusion of epinephrine 0.6 μg·kg-1·min-1 after LPS intravenous injection. Hepatic injury was evaluated by determining the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and by liver pathological examination. Blood samples were taken 0, 2 and 6 h later and the levels of serum TNF-α, IL-1β and IL-10 were detected by enzyme-linked immunoadsorbent assay (ELISA). At the same time points, the levels of serum ALT and AST were also detected. The liver pathological changes were observed at 6 h. Results In LPS group, serum levels of ALT and AST were increased significantly compared with control group (all P<0.05) at 2 h and 6 h. Pathological examination showed that LPS could cause severe congestion of hepatic sinusoids and hepatocyte necrosis. Compared with LPS group, large-dose epinephrine reduced serum levels of ALT and AST (P<0.05) and ameliorated the damage of liver tissue. In LPS group, serum levels of TNF-α, IL-1β, IL-10 were all increased compared with control group (all P<0.05). Compared with LPS group, serum levels of TNFα were significantly reduced (P<0.05), whereas IL-10 was elevated (P<0.05) in large-dose epinephrine treatment group. Serum IL-1β levels were unaffected by large-dose epinephrine treatment. Small-dose and medium-dose epinephrine could not reduce the levels of serum AST and ALT and could not reduce the liver injury induced by LPS. Compared with LPS group, levels of serum TNF-α ,IL-1β and IL-10 were also unaffected by small-dose and medium-dose epinephrine treatment( all P＞0.05) at any time points. Conclusions Epinephrine reduced the liver injury caused by LPS，down-regulated pro-inflammatory cytokines production and up-regulated anti-inflammatory cytokines production in rats. The anti-inflammatory effects may in part explain the protective effects of epinephrine on sepsis-associated liver injury. These results suggested that epinephrine may be useful in the treatment of liver injury associated with sepsis, shock, and other diseases associated with systemic inflammation.

Key words: Cytokines, Endotoxin, Epinephrine, Lipopolysaccharide, Liver, Rats