Down-regulation of Insulin-like Growth Factor I (IGF-I) in the Mouse Diaphragm during Sepsis

Background: Diaphragmatic muscle impairment is an important cause of respiratory failureduring sepsis. Insulin-like growth factor I (IGF-I) is an anabolic growthfactor which prevents muscle degradation and wasting during sepsis, but itsrole in the diaphragmatic muscle during sepsis is unknown. The aim of thisstudy was to investigate the expression of IGF-I in the diaphragmatic musclein a murine model of sepsis induced by lipopolysaccharide (LPS).Methods: Male B57 mice were peritoneally injected with LPS, and were killed andstudied at different time-points, 24 h, 48 h, 72 h, and 96 h after injection.Diaphragm sarcolemmal damage was visualized by orange tracer dye infusion,and the expression of IGF-I, interleukin-1β (IL-1β) and tumor necrosisfactor-α (TNF-α) in diaphragm tissue extracts were measured using ELISA.Results: LPS induced sarcolemmal damage in diaphragm myofibers from 24 h to 96h, which was accompanied by a significant increase in IL-1β expression inthe tissues while IGF-I levels were down-regulated. No change in TNF-αwas observed. Body weights of animals were also reduced, especially at 96h.Conclusions: The expression of IGF-I in diaphragm tissues was down-regulated duringsepsis- induced diaphragm myofiber damage, suggesting that IGF-I may bean important factor in the regulation of diaphragm myofiber repair. Furtherstudies are needed to examine the mechanisms involved.