*Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+, Maastricht; and †Department of Internal Medicine, Medisch Spectrum Twente, Enschede, the Netherlands; ‡Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany; §Department of Surgery, Atrium Medical Center, Heerlen, the Netherlands; ∥Institute of Molecular Biology, University Hospital Essen, University Duisburg-Essen, Essen, Germany; and ¶Department of Pharmacology and Toxicology, VCU Medical Center, Richmond, Virginia.
Shock. 2014 Feb;41(2):109-14. doi: 10.1097/SHK.0000000000000062.
The development of an immunosuppressive state during the protracted course of sepsis is associated with opportunistic infections and is considered to correlate with the extent of the proinflammatory response during early sepsis. Short-term intervention with enteral lipid-rich nutrition was shown to attenuate the acute inflammatory response. This study investigates the effects of lipid-rich nutrition on the immunosuppression induced by polymicrobial sepsis. Female BALB/c mice were either fasted or fed liquid lipid-rich nutrition or isocaloric control nutrition before and shortly after induction of polymicrobial sepsis through cecal ligation and puncture (CLP) or sham operation. After 4 days, mice were intranasally infected with Pseudomonas aeruginosa. Twenty-four hours after P. aeruginosa infection, fasted and control nutrition-fed CLP mice displayed a significantly higher bacterial load in the lungs than did corresponding sham-operated mice (P < 0.001 and P < 0.05, respectively). Fasted CLP mice expressed reduced pulmonary levels of proinflammatory cytokines interleukin 12 (IL-12) and interferon γ (IFN-γ) in comparison to sham mice (both P < 0.05). Lipid-rich nutrition prevented the increase in bacteria, promoted the IL-12 and IFN-γ production (IL-12 and IFN-γ [P < 0.05] vs. fasted and IFN-γ [P < 0.05] vs. control nutrition), and prevented the expression of the immunosuppressive cytokine IL-10 (P < 0.05 vs. control nutrition) in lungs of CLP mice. The preserved immune defense during late sepsis in lipid-rich fed mice was preceded by attenuation of the early inflammatory response (IL-6 [P = 0.05] and IL-10 [P < 0.01] vs. fasted CLP mice) at 6 h after CLP. In conclusion, short-term treatment with lipid-rich enteral nutrition improves the pulmonary antimicrobial defense during polymicrobial sepsis.
在脓毒症的长期病程中,免疫抑制状态的发展与机会性感染有关,并且被认为与早期脓毒症期间促炎反应的程度相关。短期肠内给予富含脂肪的营养支持被证明可以减轻急性炎症反应。本研究调查了富含脂肪的营养对多微生物脓毒症引起的免疫抑制的影响。雌性 BALB/c 小鼠在多微生物脓毒症通过盲肠结扎和穿刺(CLP)或假手术诱导之前和之后不久接受禁食或液体富含脂肪的营养或等热量对照营养。4 天后,小鼠经鼻腔感染铜绿假单胞菌。在铜绿假单胞菌感染后 24 小时,禁食和对照营养喂养的 CLP 小鼠肺部的细菌负荷明显高于相应的假手术组小鼠(P < 0.001 和 P < 0.05)。与假手术组小鼠相比,禁食 CLP 小鼠的肺部促炎细胞因子白细胞介素 12(IL-12)和干扰素 γ(IFN-γ)水平降低(均 P < 0.05)。富含脂肪的营养支持可防止细菌增加,促进 IL-12 和 IFN-γ 的产生(IL-12 和 IFN-γ [P < 0.05]与禁食和 IFN-γ [P < 0.05]与对照营养),并防止 CLP 小鼠肺部免疫抑制细胞因子 IL-10 的表达(P < 0.05 与对照营养)。富含脂肪的喂养小鼠在 CLP 后 6 小时早期炎症反应减弱(IL-6 [P = 0.05]和 IL-10 [P < 0.01]与禁食 CLP 小鼠相比),随后在晚期脓毒症中保留了免疫防御。
总之,短期给予富含脂肪的肠内营养可改善多微生物脓毒症期间肺部的抗微生物防御。