Role of IGF-I and the TNF/NF-B pathway in the induction of muscle atrogenes by acute inflammation

catabolic states (sepsis, cancer, etc.) associated with acute inflamma-tion are characterized by a loss of skeletal muscle due to accelerated proteolysis. The main proteolytic systems involved are the autophagy and the ubiquitin-proteasome (UPS) pathways. Among the signaling pathways that could mediate proteolysis induced by acute inflamma-tion, the transcription factor NF-B, induced by TNF, and the transcription factor forkhead box O (FOXO), induced by glucocorti-coids (GC) and inhibited by IGF-I, are likely to play a key role. The aim of this study was to identify the nature of the molecular mediators responsible for the induction of these muscle proteolytic systems in response to acute inflammation caused by LPS injection. LPS injec-tion robustly stimulated the expression of several components of the autophagy and the UPS pathways in the skeletal muscle. This induc-tion was associated with a rapid increase of circulating levels of TNF together with a muscular activation of NF-B followed by a decreas