Chronic septic
abscess formation causes an inhibition of
protein synthesis in gastrocnemius that is not observed in rats with a sterile
abscess. The inhibition is associated with an impaired translation initiation. The present study was designed to investigate the effects of
sepsis on the level of phosphorylated eukaryotic
initiation factor (
eIF) 4G in gastrocnemius after induction of a chronic intra-abdominal sterile or septic
abscess as a possible mechanism to account for the impairment of translation initiation during
sepsis. The extent of phosphorylated
eIF4G was reduced by more than 50% (P< 0.05) and 68% (P < 0.01) in gastrocnemius after 3 and 5 days, respectively, and returned to control values after 14 days of
abscess formation in septic rats compared with sterile inflammatory animals. To examine the mediators of the septic process contributing to the decreased levels of phosphorylated
eIF4G, the
cytokine response to
sepsis was pharmacologically modulated. First, treatment of septic rats with
tumor necrosis factor (TNF)
binding protein or
interleukin (
IL) 1 receptor antagonist increased the level of phosphorylated
eIF4G. Second, infusion of
TNF-alpha for 24 h in control rats resulted in a 70% decrease in phosphorylated
eIF4G. Third, infusion of
IL-1ra led to an increase in the level of phosphorylation of
eIF4G in rats infused with
TNF-alpha. Taken together, the data indicate that a
cytokine-dependent decrease in the steady state phosphorylation of
eIF4G is a possible mechanism accounting for the inhibition of skeletal muscle
protein synthesis during
sepsis. Furthermore, the findings support a role of
IL-1 as the proinflammatory mediator responsible for the reduced level of phosphorylated
eIF4G.