Continuous administration of enteral lipid- and protein-rich nutrition limits inflammation in a human endotoxemia model

T. Lubbers*, M. Kox, J.J. de Haan, J.W. Greve, J.C. Pompe, B.P. Ramakers, P. Pickkers, W.A. Buurman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

36 Citations (Web of Science)


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-alpha 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.
Original languageEnglish
Pages (from-to)1258-1265
Number of pages8
JournalCritical Care Medicine
Issue number5
Publication statusPublished - May 2013


  • anti-inflammatory reflex
  • endotoxin
  • enteral nutrition
  • enterocyte damage
  • systemic inflammation

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