Endotoxin-induced changes in IGF-I differ in rats provided enteral vs. parenteral nutrition

The purpose of the present study was to determine whether acute changes in the insulin-like growth factor (IGF) system induced by mild surgical trauma /fasting or endotoxin [lipopolysaccharide (LPS)] are differentially modulat ed by total enteral nutrition (TEN) or total parenteral nutrition (TPN). Ra ts had vascular catheters and a gastrostomy tube surgically placed and were fasted overnight. The next morning animals randomly received an isocaloric , isonitrogenous (250 kcal kg(-1) day(-1), 1.6 g N kg(-1) day(-1)) infusion of either TEN or TPN for 48 h. Then rats were injected intravenously with Escherichia coli LPS (I mg/kg) while nutritional support was continued. Tim e-matched control animals were injected with saline. After mild surgical tr auma and an 18-h fast, TEN was more effective at increasing plasma IGF-I le vels than TPN. Subsequent injection of LPS decreased IGF-I in blood, liver, and muscle in both TEN- and TPN-fed rats compared with saline-injected con trol animals. However, this decrease was similar to 30% greater in rats fed TPN compared with those fed TEN. LPS-induced downregulation of IGF-I mRNA expression in liver and muscle was also more prominent in TPN-fed rats. The LPS-induced increase in plasma corticosterone and tumor necrosis factor-oc was greater (2- and 1.6-fold, respectively) in TPN-fed rats, and these cha nges were consistent with the greater reduction in IGF-I seen in these anim als. In similarly treated rats allowed to survive for 24 h after LPS inject ion, the LPS-induced increase in the urinary 3-methylhistidine-to-creatinin e ratio was smaller in TEN-fed rats. In summary, LPS reduced systemic level s of IGF-I as well as IGF-I protein and mRNA in critical target organs. Ent eral feeding greatly attenuated this response. Maintenance of higher IGF-I levels in TEN-fed rats was associated with a reduction in inflammatory cyto kine levels and lower rates of myofibrillar degradation.