Down-regulation of Insulin-like Growth Factor I (IGF-I) in the Mouse Diaphragm during Sepsis Meng-Chih Lin 1,2 , MD; Sum Yee Leung 1 , MD, PhD; Wen-Feng Fang 1 , MD; Chien-Hung Chin 1 , MD; Kian Fan Chung 3 , MD, DSc Background: Diaphragmatic muscle impairment is an important cause of respiratory fai- lure 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 infu- sion, 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. (Chang Gung Med J 2010;33:501-8) Key words: diaphragm myofiber, insulin-like growth factor-I, interleukin-1β, lipopolysaccharide, sarcolemmal damage, sepsis From the 1 Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2 Department of Respiratory Care, Chang Gung Institute of Technology, Chiayi, Taiwan; 3 Thoracic Medicine, National Heart & Lung Institute, Imperial College, London, U.K. Received: June 8, 2009; Accepted: Sep. 30, 2009 Correspondence to: Dr. Meng-Chih Lin, Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital- Kaohsiung Medical Center. 123, Dapi Rd., Niaosong Township, Kaohsiung County 833, Taiwan (R.O.C.) Tel.: 886-7-7317123-8199; Fax: 886-7-7322402; E-mail: mengchih@adm.cgmh.org.tw R espiratory failure, is frequently observed in patients with severe sepsis syndrome and is a major factor contributing to the high mortality rate. (1) The diaphragm is a major primary muscle for respi- ration; diaphragm dysfunction characterized by a decrease in both diaphragmatic force production and endurance has been previously demonstrated in ani- mal models of sepsis. (2-6) An inability of the diaphragm to ventilate the lungs, rather than pul- monary involvement per se, was seen in animals dying of respiratory failure in a septic shock model. (3) Therefore, respiratory muscle dysfunction plays an 501 Original Article