TNF-binding protein ameliorates inhibition of skeletal muscle protein synthesis during sepsis

We examined the effects of TNF-binding protein (TNFBP) on regulatory mechan isms of muscle protein synthesis during sepsis in four groups of rats: Cont rol; Control+TNFBP; Septic; and Septic+TNFBP. Saline (1.0 ml) or TNFBP (1 m g/kg, 1.0 ml) was injected daily starting 4 h before the induction of sepsi s. The effect of TNFBP on gastrocnemius weight, protein content, and the ra te of protein synthesis was examined 5 days later. Sepsis reduced the rate of protein synthesis by 35% relative to controls by depressing translationa l efficiency. Decreases in protein synthesis were accompanied by Similar re ductions in protein content and muscle weight. Treatment of septic animals with TNFBP for 5 days prevented the sepsis-induced inhibition of protein sy nthesis and restored translational efficiency to control values. TNFBP trea tment of Control rats for 5 days was without effect on muscle protein conte nt or protein synthesis. We also assessed potential mechanisms regulating t ranslational efficiency. The phosphorylation state of p70(S6) kinase was no t altered by sepsis. Sepsis reduced the gastrocnemius content of eukaryotic initiation factor 2B epsilon (eIF2B epsilon), but not eIF2 alpha. The decr ease in eIF2B epsilon content was prevented by treatment of septic rats wit h TNFBP. TNFBP ameliorates the sepsis-induced changes in protein metabolism in gastrocnemius, indicating a role for TNF in the septic process. The dat a suggest that TNF may impair muscle protein synthesis by reducing expressi on of specific initiation factors during sepsis.