O'Leary Michael J, Xue Aiqun, Scarlett Christopher J, Sevette Andre, Kee Anthony J, Smith Ross C
Department of Intensive Care, The St George Hospital, Kogarah, NSW 2217, Australia.
Crit Care. 2007;11(4):R79. doi: 10.1186/cc5972.
Early nutrition is recommended for patients with sepsis, but data are conflicting regarding the optimum route of delivery. Enteral nutrition (EN), compared with parenteral nutrition (PN), results in poorer achievement of nutritional goals but may be associated with fewer infections. Mechanisms underlying differential effects of the feeding route on patient outcomes are not understood, but probably involve the immune system and the anabolic response to nutrients. We studied the effect of nutrition and the route of delivery of nutrition on cytokine profiles, the growth hormone-insulin-like growth factor-1 (IGF-I) axis and a potential mechanism for immune and anabolic system interaction, the suppressors of cytokine signaling (SOCS), in rodents with and without sepsis.
Male Sprague-Dawley rats were randomized to laparotomy (Sham) or to cecal ligation and puncture (CLP), with postoperative saline infusion (Starve), with EN or with PN for 72 hours. Serum levels of IL-6 and IL-10 were measured by immunoassay, and hepatic expressions of cytokine-inducible SH2-containing protein, SOCS-2, SOCS-3, IGF-I and the growth hormone receptor (GHR) were measured by real-time quantitative PCR.
IL-6 was detectable in all groups, but was only present in all animals receiving CLP-PN. IL-10 was detectable in all but one CLP-PN rat, one CLP-EN rat, approximately 50% of the CLP-Starve rats and no sham-operated rats. Cytokine-inducible SH2-containing protein mRNA was increased in the CLP-EN group compared with the Sham-EN group and the other CLP groups (P < 0.05). SOCS-2 mRNA was decreased in CLP-PN rats compared with Sham-PN rats (P = 0.07). SOCS-3 mRNA was increased with CLP compared with sham operation (P < 0.03). IGF-I mRNA (P < 0.05) and GHR mRNA (P < 0.03) were greater in the fed CLP animals and in the Sham-PN group compared with the starved rats.
In established sepsis, nutrition and the route of administration of nutrition influences the circulating cytokine patterns and expression of mRNA of SOCS proteins, GHR and IGF-I. The choice of the administration route of nutrition may influence cellular mechanisms that govern the response to hormones and mediators, which further influence the response to nutrients. These findings may be important in the design and analysis of clinical trials of nutritional interventions in sepsis in man.
脓毒症患者建议尽早进行营养支持，但关于最佳营养输送途径的数据存在冲突。与肠外营养（PN）相比，肠内营养（EN）在实现营养目标方面效果较差，但可能与感染较少有关。营养输送途径对患者预后产生不同影响的潜在机制尚不清楚，但可能涉及免疫系统以及对营养物质的合成代谢反应。我们研究了营养及其输送途径对细胞因子谱、生长激素 - 胰岛素样生长因子 -1（IGF -I）轴以及免疫和合成代谢系统相互作用的潜在机制——细胞因子信号转导抑制因子（SOCS）在有或无脓毒症的啮齿动物中的影响。
将雄性Sprague - Dawley大鼠随机分为接受剖腹手术（假手术组）或盲肠结扎穿刺术（CLP），术后分别给予生理盐水输注（饥饿组）、肠内营养或肠外营养72小时。通过免疫测定法测量血清白细胞介素 -6（IL -6）和白细胞介素 -10（IL -10）水平，并通过实时定量聚合酶链反应测量肝脏中细胞因子诱导含SH2蛋白、SOCS -2、SOCS -3、IGF -I和生长激素受体（GHR）的表达。
所有组均检测到IL -6，但仅在所有接受CLP - PN的动物中存在。除一只CLP - PN大鼠、一只CLP - EN大鼠、约50%的CLP - 饥饿组大鼠外，其他组均检测到IL -10，假手术组大鼠未检测到。与假手术 - EN组和其他CLP组相比，CLP - EN组中细胞因子诱导含SH2蛋白的信使核糖核酸（mRNA）增加（P < 0.05）。与假手术 - PN组相比，CLP - PN大鼠中SOCS -2 mRNA降低（P = 0.07）。与假手术相比，CLP组中SOCS -3 mRNA增加（P < 0.03）。与饥饿大鼠相比，接受喂养的CLP动物和假手术 - PN组中的IGF -I mRNA（P < 0.05）和GHR mRNA（P < 0.03）更高。
在已确诊的脓毒症中，营养及其给药途径会影响循环细胞因子模式以及SOCS蛋白、GHR和IGF -I的mRNA表达。营养给药途径的选择可能会影响控制对激素和介质反应的细胞机制，进而进一步影响对营养物质的反应。这些发现可能对人类脓毒症营养干预临床试验的设计和分析具有重要意义。
