pattismith
Senior Member
- Messages
- 3,941
Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans
Author links open overlay panelJulieLasselinabc1BiankaKarshikoffbd1JohnAxelssonbcTorbjörnÅkerstedtbcSvenBensonaHaraldEngleraManfredSchedlowskiaMikeJoneseMatsLekanderbcdAnnaAndreassonceaInstitute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45 122 Essen, GermanybDepartment of Clinical Neuroscience, Karolinska Institutet, Nobels väg 9, 171 65 Solna, Stockholm, SwedencStress Research Institute, Stockholm University, Frescati Hagväg 16A, 106 91 Stockholm, SwedendOsher Center for Integrative Medicine, Karolinska Institutet, Nobels väg 9, 171 65 Solna, Stockholm, SwedeneDepartment of Psychology, Macquarie University, North Ryde, NSW, Australia
Received 30 April 2019, Revised 28 October 2019, Accepted 30 October 2019, Available online 1 November 2019.
Show less
Add to Mendeley
Share
Cite
https://doi.org/10.1016/j.bbi.2019.10.020Get rights and content
Highlights
•
We used pooled data to examine the dynamic of the fatigue response to inflammation.
•
Sleepiness was also assessed as it is a symptom distinct from fatigue.
•
The development of fatigue and sleepiness paralleled the cytokine response.
•
A stronger cytokine response was related to developing more fatigue and sleepiness.
•
There was no moderation effect of baseline inflammatory status.
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.
Author links open overlay panelJulieLasselinabc1BiankaKarshikoffbd1JohnAxelssonbcTorbjörnÅkerstedtbcSvenBensonaHaraldEngleraManfredSchedlowskiaMikeJoneseMatsLekanderbcdAnnaAndreassonceaInstitute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45 122 Essen, GermanybDepartment of Clinical Neuroscience, Karolinska Institutet, Nobels väg 9, 171 65 Solna, Stockholm, SwedencStress Research Institute, Stockholm University, Frescati Hagväg 16A, 106 91 Stockholm, SwedendOsher Center for Integrative Medicine, Karolinska Institutet, Nobels väg 9, 171 65 Solna, Stockholm, SwedeneDepartment of Psychology, Macquarie University, North Ryde, NSW, Australia
Received 30 April 2019, Revised 28 October 2019, Accepted 30 October 2019, Available online 1 November 2019.
Show less
Add to Mendeley
Share
Cite
https://doi.org/10.1016/j.bbi.2019.10.020Get rights and content
Highlights
•
We used pooled data to examine the dynamic of the fatigue response to inflammation.
•
Sleepiness was also assessed as it is a symptom distinct from fatigue.
•
The development of fatigue and sleepiness paralleled the cytokine response.
•
A stronger cytokine response was related to developing more fatigue and sleepiness.
•
There was no moderation effect of baseline inflammatory status.
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.
