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

Robert N. Cooney, Scot R. Kimball, George Maish, Margaret Shumate, Thomas C. Vary

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background. Cytokines are thought to play a role in the stimulation of protein synthesis in liver during inflammation and sepsis. We previously showed that administration of tumor necrosis factor-binding protein (TNFbp) prevents the sepsis-induced inhibition of protein synthesis in skeletal muscle. The purpose of the present set of experiments was to investigate the effect of TNFbp on hepatic protein synthesis and its ability to modulate the mechanisms 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, septic, and septic + TNFbp. Saline (1.0 ml) or TNFbp (1 mg/kg, 1.0 ml) was injected daily starting 4 h prior to the induction of sepsis. The effect of sepsis and TNFbp administration on hepatic protein synthesis in vivo was examined 5 days later. Results. Sepsis increased the rate of protein synthesis by 35% relative to controls. Accelerated rates of protein synthesis were accompanied by increased total RNA content, eukaryotic initiation factor (eIF) 2α content, and phosphorylation of p70S6 kinase. Injection of TNFbp into septic rats for 5 days did not diminish the sepsis-induced stimulation of hepatic protein synthesis. Compared with controls, septic rats treated with TNFbp also showed elevated total RNA content, elF2α 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 parameters examined. Conclusions. TNFbp did not prevent the sepsis-induced stimulation of hepatic protein metabolism or modulate the septic-induced changes in factors regulating protein synthesis. Global rates of protein synthesis in livers from septic rats are accelerated by increases in the abundance or activity of components of translational apparatus. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalJournal of Surgical Research
Volume93
Issue number2
DOIs
StatePublished - 2000

All Science Journal Classification (ASJC) codes

  • Surgery

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