Regulation of skeletal muscle protein turnover during sepsis: mechanisms and mediators.
Skeletal muscle protein wasting is a prominent feature of the metabolic response to sepsis. Persistent protein wasting leads to muscle dysfunction and prolongs recovery from the septic insult. Unfortunately, conventional nutritional support alone does not prevent the sepsis-induced weight loss and catabolism of muscle. Hence, mechanisms other than substrate deficiency appear to be involved in the derangements in protein metabolism during sepsis. The catabolism of muscle during sepsis results from a stimulation of proteolysis and an inhibition of protein synthesis. This review summarizes the mechanisms responsible for alterations in protein synthesis and degradation in muscle during sepsis at the biochemical level. The ability of hormones (insulin, insulin-like growth factor I, glucocorticoids) or cytokines (tumor necrosis factor, interleukin-1) to act as mediators of protein catabolism is also examined. Finally, we discuss the potential role of anticytokine therapies in preventing derangements in protein metabolism during sepsis. A picture is emerging which suggests that cytokines may influence skeletal muscle protein metabolism during sepsis both indirectly through inhibition of the regulatory actions of anabolic hormones on protein turnover, and directly through modulation of the protein synthesis and degradation enzymatic machinery.
Cooney
R N
RN
Department of Surgery, Pennsylvania State University, College of Medicine, Hershey 17033, USA.
Kimball
S R
SR
Vary
T C
TC
D000818:Animals; D016207:Cytokines / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D008954:Models, Biological; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010442:Peptide Chain Initiation, Translational; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism*
D016207:Cytokines; D020662:Guanine Nucleotide Exchange Factors; D009124:Muscle Proteins; D011500:Protein Synthesis Inhibitors; D011506:Proteins