Endotoxemia-induced inflammation and the effect on the human brain
Open accessAbstract
Introduction: Effects of systemic inflammation on cerebral function are not clear, as both inflammation-induced encephalopathy as well as stress-hormone mediated alertness have been described. Methods: Experimental endotoxemia (2 ng/kg Escherichia coli lipopolysaccharide [LPS]) was induced in 15 subjects, whereas 10 served as controls. Cytokines (TNF-α, IL-6, IL1-RA and IL-10), cortisol, brain specific proteins (BSP), electroencephalography (EEG) and cognitive function tests (CFTs) were determined. Results: Following LPS infusion, circulating pro- and anti-inflammatory cytokines, and cortisol increased (P < 0.0001). BSP changes stayed within the normal range, in which neuron specific enolase (NSE) and S100-β changed significantly. Except in one subject with a mild encephalopathic episode, without cognitive dysfunction, endotoxemia induced no clinically relevant EEG changes. Quantitative EEG analysis showed a higher state of alertness detected by changes in the central region, and peak frequency in the occipital region. Improved CFTs during endotoxemia was found to be due to a practice effect as CFTs improved to the same extent in the reference group. Cortisol significantly correlated with a higher state of alertness detected on the EEG. Increased IL-10 and the decreased NSE both correlated with improvement of working memory and with psychomotor speed capacity. No other significant correlations between cytokines, cortisol, EEG, CFT and BSP were found. Conclusions: Short-term systemic inflammation does not provoke or explain the occurrence of septic encephalopathy, but primarily results in an inflammation-mediated increase in cortisol and alertness. Trial registration: NCT00513110.
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Stroop performance was not impaired after low-dose (0.4 ng/mL) or high-dose (2.0 ng/mL) endotoxin administration.
“Stroop performance was not impaired after endotoxin administration at either a low dose (0.4 ng/mL) (Grigoleit et al., 2010) or high dose (2.0 ng/mL) (van den Boogaard et al., 2010).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as van den Boogaard et al., 2010
Data in humans so far reported inconsistent results of experimental endotoxemia with a significant improvement or no effect on working memory.
“However, data in humans so far reported inconsistent results of experimental endotoxemia with a significant improvement [24] or no effect on working memory [25], [27].”
From Dose-dependent effects of endotoxin on neurobehavioral functions in humans (2011) · cites this paper as [27]
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- Authors
- van den Boogaard, M., Ramakers, B. P., van Alfen, N., van der Werf, S. P., Fick, W. F., Hoedemaekers, C. W., Verbeek, M. M., Schoonhoven, L., van der Hoeven, J. G., & Pickkers, P.
- Affiliations
- Radboud University Medical Center (NL)
- Venue
- Critical Care
- Published
- 2010-05-05
- Volume
- 14
- Issue
- 3
- Pages
- R81-R81
- ISSN
- 1364-8535 (ISSN-L)
- PMC
- PMC2911704
- OpenAlex
- W2115219775
- Cited by
- 84
- References
- 47
- Citations by year
- 2025: 5 · 2024: 9 · 2023: 7 · 2022: 1 · 2021: 9 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 7 · 2016: 3 · 2015: 5 · 2014: 3 · 2013: 8 · 2012: 8
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Critical Care (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- endotoxemia, lipopolysaccharide, systemic inflammation, sepsis-associated encephalopathy, brain-specific proteins, neuron-specific enolase, S100β, cortisol, alertness, EEG, cognitive function, working memory, psychomotor speed, cytokines, IL-10, TNF-α, interleukin-6, interleukin-1 receptor antagonist
- MeSH terms
- Adult, Brain, Brain Diseases, Clinical Trials as Topic, Cognition, Electroencephalography, Escherichia coli, Humans, Hydrocortisone, Inflammation, Lipopolysaccharides, Male, Cytokines, Endotoxemia, Young Adult
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