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 failure during sepsis. Insulin-like growth factor I (IGF-I) is an anabolic growth factor which prevents muscle degradation and wasting during sepsis, but its role in the diaphragmatic muscle during sepsis is unknown. The aim of this study was to investigate the expression of IGF-I in the diaphragmatic muscle in a murine model of sepsis induced by lipopolysaccharide (LPS). Methods: Male B57 mice were peritoneally injected with LPS, and were killed and studied 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 necrosis factor-α (TNF-α) in diaphragm tissue extracts were measured using ELISA. Results: LPS induced sarcolemmal damage in diaphragm myofibers from 24 h to 96 h, which was accompanied by a significant increase in IL-1β expression in the tissues while IGF-I levels were down-regulated. No change in TNF-α was observed. Body weights of animals were also reduced, especially at 96 h. Conclusions: The expression of IGF-I in diaphragm tissues was down-regulated during sepsis- induced diaphragm myofiber damage, suggesting that IGF-I may be an important factor in the regulation of diaphragm myofiber repair. Further studies are needed to examine the mechanisms involved.