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Endotoxemia-induced inflammation and the effect on the human brain

Endotoxemia-induced inflammation and the effect on the human brain
Endotoxemia-induced inflammation and the effect on the human brain
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-?, 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-? 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.
1364-8535
R81-[9pp]
Van den Boogaard, Mark
4751824c-6a51-4bc8-8854-97f4579e045b
Ramakers, Bart P.
4d2ab8ae-d166-4a2b-a646-cae3c6cd10c3
van Alfen, Nens
3895bc70-ad8e-466a-9633-9944fc0ae298
van der Werf, Sieberen P.
d68ca67e-e29d-48b4-b1cc-a3d4fcef1cf8
Fick, Wilhelmina F.
3f854cfe-ce0d-4938-bfdc-312f6d4c8a56
Hoedemaekers, Cornelia W.
c117d67b-7858-4efd-87d9-a5a5b6b378e5
Verbeek, Marcel M.
c21991ca-081f-4249-9c88-ba1a94b58b3f
Schoonhoven, Lisette
46a2705b-c657-409b-b9da-329d5b1b02de
van der Hoeven, Johannes G.
78ca86cf-76cd-4578-b063-649414423b43
Pickkers, Peter
516df191-7ae2-457e-a7f7-abd6ca935687
Van den Boogaard, Mark
4751824c-6a51-4bc8-8854-97f4579e045b
Ramakers, Bart P.
4d2ab8ae-d166-4a2b-a646-cae3c6cd10c3
van Alfen, Nens
3895bc70-ad8e-466a-9633-9944fc0ae298
van der Werf, Sieberen P.
d68ca67e-e29d-48b4-b1cc-a3d4fcef1cf8
Fick, Wilhelmina F.
3f854cfe-ce0d-4938-bfdc-312f6d4c8a56
Hoedemaekers, Cornelia W.
c117d67b-7858-4efd-87d9-a5a5b6b378e5
Verbeek, Marcel M.
c21991ca-081f-4249-9c88-ba1a94b58b3f
Schoonhoven, Lisette
46a2705b-c657-409b-b9da-329d5b1b02de
van der Hoeven, Johannes G.
78ca86cf-76cd-4578-b063-649414423b43
Pickkers, Peter
516df191-7ae2-457e-a7f7-abd6ca935687

Van den Boogaard, Mark, Ramakers, Bart P., van Alfen, Nens, van der Werf, Sieberen P., Fick, Wilhelmina F., Hoedemaekers, Cornelia W., Verbeek, Marcel M., Schoonhoven, Lisette, van der Hoeven, Johannes G. and Pickkers, Peter (2010) Endotoxemia-induced inflammation and the effect on the human brain. Critical Care, 14 (3), R81-[9pp]. (doi:10.1186/cc9001). (PMID:20444270)

Record type: Article

Abstract

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-?, 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-? 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.

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Published date: May 2010
Organisations: Faculty of Health Sciences

Identifiers

Local EPrints ID: 339218
URI: http://eprints.soton.ac.uk/id/eprint/339218
ISSN: 1364-8535
PURE UUID: cabaf12c-e749-4918-b037-d49dfb239bec
ORCID for Lisette Schoonhoven: ORCID iD orcid.org/0000-0002-7129-3766

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Date deposited: 25 May 2012 10:34
Last modified: 15 Mar 2024 03:41

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Contributors

Author: Mark Van den Boogaard
Author: Bart P. Ramakers
Author: Nens van Alfen
Author: Sieberen P. van der Werf
Author: Wilhelmina F. Fick
Author: Cornelia W. Hoedemaekers
Author: Marcel M. Verbeek
Author: Johannes G. van der Hoeven
Author: Peter Pickkers

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