Effect of central administration of interleukin-1 receptor antagonist on protein synthesis in skeletal muscle, kidney, and liver during sepsis

Inflammatory cytokines may mediate the host response to infection via central nervous system (CNS), endocrine, and/or paracrine pathways. The purpose of the present study was to determine whether intracerebroventricular (ICV) infusion of interleukin-1 receptor antagonist (IL-1ra) influences the effects of sepsis on protein metabolism in peripheral organs (skeletal muscle, kidney, and liver). A constant ICV infusion of IL-1ra (100 mug/h) or saline was begun immediately before the induction of sepsis or sterile inflammation and continued for 5 days. ICV infusion of IL-1ra did not alter protein metabolism in animals with a sterile abscess. Sepsis reduced muscle weight, protein content, and rates of protein synthesis in gastrocnemius. ICV infusion of IL-1ra attenuated the sepsis-induced loss of muscle mass and protein and the inhibition of protein synthesis in gastrocnemius by augmenting the translational efficiency. Similar results were observed in kidney, with respect to kidney weight, total protein, rates of protein synthesis, and translational efficiency. However, central infusion of IL-1ra did result in a small (12%) increase in the renal RNA content in either sterile or septic abscess rats. In liver, ICV infusion of IL-1ra prevented the sepsis-induced inhibition of protein synthesis and reduction in translational efficiency. These results suggest that central administration IL-1ra can modulate protein metabolism in peripheral organs during sepsis by preventing the sepsis-induced defects in the translational efficiency. (C) 2003 Elsevier Inc. All rights reserved.