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Critical Care Medicine:
doi: 10.1097/CCM.0b013e31827c0a17
Laboratory Investigations

Continuous Administration of Enteral Lipid- and Protein-Rich Nutrition Limits Inflammation in a Human Endotoxemia Model

Lubbers, Tim MD, PhD1; Kox, Matthijs PhD2,3; de Haan, Jacco-Juri MD1; Greve, Jan Willem MD, PhD4; Pompe, Jan C. MD2; Ramakers, Bart P. MD2; Pickkers, Peter MD, PhD2; Buurman, Wim A. PhD1

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Objective: An overzealous inflammatory response is an important cause of morbidity and mortality in surgical, trauma, and critically ill patients. Enteral administration of lipid-rich nutrition was previously shown to attenuate inflammation and reduce organ damage via a cholecystokinin-1 receptor–mediated vagovagal reflex in animal studies. The current preclinical study investigates the immunomodulatory potential of a custom-made enteral nutrition during systemic inflammation in man.

Design: Double-blind, randomized controlled trial.

Setting: Intensive care research unit.

Subjects: Male volunteers.

Interventions: After an overnight fast, 18 healthy male subjects received an IV bolus of Escherichia coli lipopolysaccharide (2 ng/kg). Subjects in the fasted group (n = 6) were deprived of food throughout the study, while subjects in the intervention groups were fed either custom-made lipid- and protein-rich nutrition (n = 6) or isocaloric control nutrition (n = 6) via nasojejunal tube, starting 1 hour prior to lipopolysaccharide administration until 6 hours afterward.

Measurements and Main Results: Bolus lipopolysaccharide administration resulted in a marked inflammatory response. Continuous postpyloric administration of nutrition significantly increased plasma cholecystokinin levels throughout the lipopolysaccharide-induced inflammatory response. Lipid- and protein-rich nutrition attenuated circulating levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and the interleukin-1 receptor antagonist compared with control nutrition (all p < 0.05) and fasted subjects (all p < 0.05). In additional, lipid- and protein-rich nutrition augmented the anti-inflammatory response, reflected by increased plasma levels of interleukin-10 compared with fasted subjects (p < 0.0001).

Conclusions: The current preclinical study expands the immunomodulating effects of enteral nutrition as previously observed in rodents to man. Continuous administration of enteral nutrition resulted in a rapid anti-inflammatory effect. Furthermore, enrichment of the nutritional composition with lipid and protein was shown to enhance the anti-inflammatory potential. Therefore, continuous enteral administration of lipid- and protein-rich nutrition is a promising intervention to modulate the immune response in the early course of systemic inflammation in man.

© 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

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