Low-dose endotoxemia and human neuropsychological functions

Karen Suárez Krabbe, Abraham Reichenberg, Raz Yirmiya, Annelise Smed, Bente Klarlund Pedersen, Helle Bruunsgaard

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157 Scopus citations


Epidemiological data demonstrate an association between systemic low-grade inflammation defined as 2- to 3-fold increases in circulating inflammatory mediators and age-related decline in cognitive function. However, it is not known whether small elevations of circulating cytokine levels cause direct effects on human neuropsychological functions. We investigated changes in emotional, cognitive, and inflammatory parameters in an experimental in vivo model of low-grade inflammation. In a double-blind crossover study, 12 healthy young males completed neuropsychological tests before as well as 1.5, 6, and 24 h after an intravenous injection of Escherichia coli endotoxin (0.2 ng/kg) or saline in two experimental sessions. Endotoxin administration had no effect on body temperature, cortisol levels, blood pressure or heart rate, but circulating levels of tumor necrosis factor (TNF) and interleukin (IL)-6 increased 2- and 7-fold, respectively, reaching peak values at 3 h, whereas soluble TNF-receptors and IL-1 receptor antagonist peaked at 4.5 h. The neutrophil count increased and the lymphocyte count declined. In this model, low-dose endotoxemia did not affect cognitive performance significantly but declarative memory performance was inversely correlated with cytokine increases. In conclusion, our findings demonstrate a negative association between circulating IL-6 and memory functions during very low-dose endotoxemia independently of physical stress symptoms, and the hypothalamo-pituitary-adrenal axis.

Original languageAmerican English
Pages (from-to)453-460
Number of pages8
JournalBrain, Behavior, and Immunity
Issue number5
StatePublished - Sep 2005

Bibliographical note

Funding Information:
The study was supported by grants from the Danish Medical Research Council (22-02-0261) and (22-01-0019); Centre of Inflammation and Metabolism, Department of Infectious Diseases and Copenhagen Muscle Research Centre, Rigshospitalet, Faculty of Health, University of Copenhagen; Apotekerfonden af 1991; the Augustinus Foundation; the Lundbeck Foundation: the Novo Nordisk Foundation; the Velux Foundation. The Centre of Inflammation and Metabolism is supported by a grant from the Danish National Research Foundation. The Copenhagen Muscle Research Center is supported by The University of Copenhagen, The Faculties of Science and of Health Sciences at this University and The Copenhagen Hospital Corporation.


  • Cognitive function
  • Cytokines
  • Endotoxin
  • Inflammation


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