Modulation of cytokine production and its effects on metabolism and immune responsiveness in surgical stress.

我们研究了1）前期营养途径，2）外源性生长激素（GH）和胰岛素样生长因子I（IGF-I），和3）一氧化氮合酶抑制剂（NAME）的管理细胞因子的产生和随后的影响的调制。4)我们还研究了生长激素对肝硬化氮代谢的影响减弱的机制，使用northem印迹分析。方法1）大鼠经全肠外营养（TPN）或全肠内营养（TEN）喂养一周后，腹腔注射3 × 10^8大肠杆菌进行攻击。2）皮下注射GH 6天后，（4.8 mg/kg/天），IGF-I腹腔注射NAME（24 mg/kg/天）或生理盐水后，用10^8大肠杆菌攻击小鼠。3）腹腔注射NAME后1小时（100 mg/kg）或生理盐水，小鼠腹腔注射10^8大肠杆菌。4)正常组和脾虚组大鼠术后给予GH（0.8IU/kg/d）或生理盐水，连续3天。结果1）TEN可提高小鼠存活率，增加腹膜渗出细胞（PEC）数量，增强免疫原性。 关于我们 在激发后2小时，随着局部TNF产生的增加而清除，同时抑制全身TNF反应。2)GH和IGF-I改善了存活率，增加了PEC数量和腹膜腔和肝脏的细菌清除率，同时抑制了TNF、IL-1和IL-6的过度全身产生。3)在细菌接种后4小时，与对照组相比，给予NAME导致存活时间缩短，腹腔内细菌数量增加，全身TNF产生增加。4)正常大鼠接受GH后，肝脏IGF-I-mRNA和血浆IGF-I水平升高，而感染大鼠即使接受GH后，肝脏IGF-I-mRNA和血浆IGF-I水平也未升高。结论1，2）与肠外营养相比，肠内营养可调节细胞因子的反应，增强感染后细菌的清除。外源性GH和IGF-I也对细胞因子的产生调节作用，并提高细菌的杀伤力。肠内营养的这些作用以及GH和IGF-I的预处理改善了宿主的防御能力，并可能阻止术后腹腔感染的发展和进展。3）另一方面，使用NAME抑制一氧化氮的产生，在这种革兰氏阴性脓毒症模型中产生有害作用。4)手术后给予生长激素不会增加肝硬化患者肝脏IGF-I-mRNA和血浆IGF-I水平。因此，在肝硬化患者中，外源性IGF-I可能比GH更有效地改善手术后的氮代谢。少

We investigated modulation of cytokine production and consequent effects by 1) antecedent nutritional routes, 2) exogenous growth hormone (GH) and insulin-like growth factor I (IGF-I), and 3) administration of a nitric oxide synthase inhibitor (NAME). 4) We also studied the mechanism by which effects of GH on nitrogen metabolism are attenuated in cirrhosis, using northem blot analysis. Method 1) Rats were fed through total parenteral nutrition (TPN) or total enteral nutrition (TEN) for a week, and then challenged i.p.with 3*10^8 E.coli.2) After six days of s.c.treatments with GH (4.8mg/kg/day), IGF-I (24mg/kg/day) or saline, mice were challenged i.p.with 10^8 E.coli.3) One hour after i.p.treatment with NAME (100mg/kg) or saline, mice were challenged i.p.with 10^8 E.coli. 4) Normal and cirrhotic rats received GH (0.8IU/kg/day) or saline for 3 postoperative days after gastrectomy. Results 1) TEN improved survival, increased numbers of peritoneal exudative cells (PEC) and enhanced bacteri … More al clearance with increased local TNF production, while suppressing systemic TNF response, at 2 hours after challenge. 2) GH and IGF-I improved survival, increased PEC numbers and bacterial clearance from peritoneal cavity and liver, while suppressing excessive systemic production of TNF,IL-1 and IL-6, at 6 hours after challenge. 3) Administration of NAME resulted in poor survival times, increases in bacterial numbers in the peritoneal cavity, and an increase in systemic TNF production compared with controls, at four hours after bacterial inoculation. 4) Liver IGF-I-mRNA and plasma IGF-I level were increased in normal rats that received GH,although these values were not increased in cirrhotic rats even if they received GH.Conclusions 1,2) Antecedent enteral nutrition modulates cytokine responses and enhances bacterial clearance after infection, as compared to parenteral nutrition. Exogenous GH and IGF-I also exerts modulatory effects on cytokine production and improves killing of bacteria. These effects of antecedent enteral nutrition, and pretreatment with GH and IGF-I,improve host defense and may prevent the development and progression of postoperative intraperitoneal infection.3) On the other hand, inhibition of nitric oxide production, using NAME,produces detrimental effects in this gram-negative sepsis model. 4) GH administration after surgery does not increase both liver IGF-I-mRNA and plasma IGF-I level in cirrhosis. Therefore, in cirrhosis, exogenous IGF-I may be more effective than GH to improve nitrogen metabolism after surgery. Less