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Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans
Stockholm University, Faculty of Social Sciences, Stress Research Institute. University of Duisburg-Essen, Germany; Karolinska Institutet, Sweden.ORCID iD: 0000-0001-8323-0714
Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
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Number of Authors: 102020 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 83, p. 309-314Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2020. Vol. 83, p. 309-314
Keywords [en]
Central fatigue, Sleepiness, Inflammation, Lipopolysaccharide, Interleukin-6, Tumor necrosis factor-alpha
National Category
Neurosciences Immunology in the medical area
Identifiers
URN: urn:nbn:se:su:diva-178654DOI: 10.1016/j.bbi.2019.10.020ISI: 000504374700034PubMedID: 31682972OAI: oai:DiVA.org:su-178654DiVA, id: diva2:1394541
Available from: 2020-02-19 Created: 2020-02-19 Last updated: 2020-03-05Bibliographically approved

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