Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans

Julie Lasselin, Bianka Karshikoff, John Axelsson, Torbjörn Åkerstedt, Sven Benson, Harald Engler, Manfred Schedlowski, Mike Jones, Mats Lekander, Anna Andreasson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Inflammation is believed to be a central mechanism in the pathophysiology of fatigue. While it is likely that dynamic of the fatigue response after an immune challenge relates to the corresponding cytokine release, this lacks evidence. Although both fatigue and sleepiness are strong signals to rest, they constitute distinct symptoms which are not necessarily associated, and sleepiness in relation to inflammation has been rarely investigated. Here, we have assessed the effect of an experimental immune challenge (administration of lipopolysaccharide, LPS) on the development of both fatigue and sleepiness, and the associations between increases in cytokine concentrations, fatigue and sleepiness, in healthy volunteers. In addition, because chronic-low grade inflammation may represent a risk factor for fatigue, we tested whether higher baseline levels of inflammation result in a more pronounced development of cytokine-induced fatigue and sleepiness. Data from four experimental studies was combined, giving a total of 120 subjects (LPS N = 79, 18 (23%) women; Placebo N = 69, 12 (17%) women). Administration of LPS resulted in a stronger increase in fatigue and sleepiness compared to the placebo condition, and the development of both fatigue and sleepiness closely paralleled the cytokine responses. Individuals with stronger increases in cytokine concentrations after LPS administration also suffered more from fatigue and sleepiness (N = 75), independent of gender. However, there was no support for the hypothesis that higher baseline inflammatory markers moderated the responses in fatigue or sleepiness after an inflammatory challenge. The results demonstrate a tight connection between the acute inflammatory response and development of both fatigue and sleepiness, and motivates further investigation of the involvement of inflammation in the pathophysiology of central fatigue.

LanguageEnglish
Pages309-314
Number of pages6
JournalBrain, Behavior, and Immunity
Volume83
DOIs
Publication statusPublished - Jan 2020

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Fatigue
Inflammation
Lipopolysaccharides
Cytokines
Placebos
Healthy Volunteers

Keywords

  • central fatigue
  • sleepiness
  • inflammation
  • lipopolysaccharide
  • interleukin-6
  • tumor necrosis factor-α

Cite this

Lasselin, Julie ; Karshikoff, Bianka ; Axelsson, John ; Åkerstedt, Torbjörn ; Benson, Sven ; Engler, Harald ; Schedlowski, Manfred ; Jones, Mike ; Lekander, Mats ; Andreasson, Anna. / Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans. In: Brain, Behavior, and Immunity. 2020 ; Vol. 83. pp. 309-314.
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Lasselin, J, Karshikoff, B, Axelsson, J, Åkerstedt, T, Benson, S, Engler, H, Schedlowski, M, Jones, M, Lekander, M & Andreasson, A 2020, 'Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans', Brain, Behavior, and Immunity, vol. 83, pp. 309-314. https://doi.org/10.1016/j.bbi.2019.10.020

Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans. / Lasselin, Julie; Karshikoff, Bianka; Axelsson, John; Åkerstedt, Torbjörn; Benson, Sven; Engler, Harald; Schedlowski, Manfred; Jones, Mike; Lekander, Mats; Andreasson, Anna.

In: Brain, Behavior, and Immunity, Vol. 83, 01.2020, p. 309-314.

Research output: Contribution to journalArticleResearchpeer-review

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