Interleukin-1 receptor antagonist prevents sepsis-induced inhibition of protein synthesis

To understand the role of interleukin-1 (IL-1) as a mediator of the sepsis-induced skeletal muscle catabolism, we investigated the effects of a specific IL-1 receptor antagonist (IL-1ra) on skeletal muscle protein metabolism in a rodent model of chronic abdominal sepsis. A constant infusion of IL-1ra (2 mg.kg-1.h-1) or saline was begun immediately after the induction of sepsis and continued for 5 days. The effect of IL-1ra on protein metabolism was examined in individual muscles (gastrocnemius, soleus, heart) containing different fiber types. Infusion of IL-1ra in control animals did not alter protein metabolism in any of the muscles examined. Muscle weight, protein content, and the rate of protein synthesis in gastrocnemius were reduced by sepsis, whereas none of these parameters were affected in soleus or heart. Infusion of IL-1ra prevented the sepsis-induced loss of muscle protein and inhibition of protein synthesis in gastrocnemius but was without effect in soleus or heart. IL-1ra infusion restored translational efficiency in the gastrocnemius of septic rats and was without effect on the RNA content. These results provide evidence for a role of IL-1 as a mediator of the sepsis-induced abnormalities in skeletal muscle protein metabolism.