Effects of tumor necrosis factor-binding protein on hepatic protein synthesis during chronic sepsis

Background Cytokines are thought to play a role in the stimulation of prote in synthesis in liver during inflammation and sepsis. We previously showed that administration of tumor necrosis factor-binding protein (TNFbp) preven ts the sepsis-induced inhibition of protein synthesis in skeletal muscle. T he purpose of the present set of experiments was to investigate the effect of TNFbp on hepatic protein synthesis and its ability to modulate the mecha nisms responsible for increased hepatic protein synthesis during chronic (5 -day) intraabdominal sepsis. Materials and methods. We examined the effects of TNFbp on hepatic protein synthesis during sepsis in four groups of rats: control, control + TNFbp, s eptic, and septic + TNFbp. Saline (1.0 ml) or TNFbp (1 mg/kg, 1.0 mi) was i njected daily starting 4 h prior to the induction of sepsis. The effect of sepsis and TNFbp administration on hepatic protein synthesis in vivo was ex amined 5 days later. Results. Sepsis increased the rate of protein synthesis by 35% relative to controls. Accelerated rates of protein synthesis were accompanied by increa sed total RNA content, eukaryotic initiation factor (eIF) 2 alpha content, and phosphorylation of p70S6 kinase. Injection of TNFbp into septic rats fo r 5 days did not diminish the sepsis-induced stimulation of hepatic protein synthesis. Compared with controls, septic rats treated with TNFbp also sho wed elevated total RNA content, elF2 alpha content, and phosphorylation of p70S6 kinase. No significant differences in any of the parameters measured were observed between untreated and TNFbp-treated septic rats. Treatment of control animals with TNFbp for 5 days was without effect on any of the par ameters examined. Conclusions. TNFbp did not prevent the sepsis-induced stimulation of hepati c protein metabolism or modulate the septic-induced changes in factors regu lating protein synthesis. Global rates of protein syn thesis in livers from septic rats are accelerated by increases in the abundance or activity of c omponents of translational apparatus. (C) 2000 Academic Press.