Biological mechanisms of chronic fatigue

Norheim, Katrine Brække; Jonsson, Grete; Omdal, Roald

doi:10.1093/rheumatology/keq454

Cited by 190 publications

(188 citation statements)

References 156 publications

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“…Taken together, our results thereby differ from findings in noninflammatory chronic pain conditions in humans, where IL-1β levels in CSF showed a positive correlation with pain assessments (34). Our observations support earlier data indicating that IL-1β is involved in the mechanisms leading to fatigue (17), which seem to be differentiated from pain in the context of RA.…”

Section: Discussionsupporting

confidence: 92%

“…Second, pain elicited by compression of the metacarpophalangeal joints of RA patients is rapidly reduced after administration of TNF blockade and associated with changes in CNS functional MRI signals (16). Third, RA is associated with increased prevalence of severe fatigue, which is also reported in a number of other diseases associated with systemic inflammation (17) and is linked to IL-1β-dependent sickness behavior in systemically inflamed rodents (18). In addition, cytokineblocking treatments targeting TNF or IL-1β are known to partly decrease fatigue symptoms in RA (19,20).…”

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confidence: 99%

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Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice

Lampa

Westman

Kadetoff

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

138

103

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During peripheral immune activation caused by an infection or an inflammatory condition, the innate immune response signals to the brain and causes an up-regulation of central nervous system (CNS) cytokine production. Central actions of proinflammatory cytokines, in particular IL-1β, are pivotal for the induction of fever and fatigue. In the present study, the influence of peripheral chronic joint inflammatory disease in rheumatoid arthritis (RA) on CNS inflammation was investigated. Intrathecal interleukin (IL)-1β concentrations were markedly elevated in RA patients compared with controls or with patients with multiple sclerosis. Conversely, the anti-inflammatory IL-1 receptor antagonist and IL-4 were decreased in RA cerebrospinal fluid (CSF). Tumor necrosis factor and IL-6 levels in the CSF did not differ between patients and controls. Concerning IL-1β, CSF concentrations in RA patients were higher than in serum, indicating local production in the CNS, and there was a positive correlation between CSF IL-1β and fatigue assessments. Next, spinal inflammation in experimental arthritis was investigated. A marked increase of IL-1β, IL-18, and tumor necrosis factor, but not IL-6 mRNA production, in the spinal cord was observed, coinciding with increased arthritis scores in the KBxN serum transfer model. These data provide evidence that peripheral inflammation such as arthritis is associated with an immunological activation in the CNS in both humans and mice, suggesting a possible therapeutic target for centrally affecting conditions as fatigue in chronic inflammatory diseases, for which to date there are no specific treatments.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice

Lampa

Westman

Kadetoff

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

138

103

View full text Add to dashboard Cite

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“…In addition, due to the loss of glucocorticoid regulation of the immune system, hypocortisolaemia can lead to an increase in pro-inflammatory cytokines [12]. An increase in proinflammatory cytokines is, in turn, associated with a range of pathophysiological and psychopathological disturbances marked by chronic fatigue [13]. It is of interest to note the many disturbances for which an association have been reported between stress, fatigue, inflammatory cytokines and dysregulation of the HPA-axis, e.g., severe burnout, chronic fatigue syndrome, fibromyalgia, atypical depression, and sickness behaviour (12,14,15,16,17,18].…”

Section: Introductionmentioning

confidence: 99%

Cynicism as subscale of burnout

Viljoen

Claassen

2017

WOR

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Background: Cynicism, as a personality trait, has adverse effects on health. The question was asked whether cynical attitudes that develop due to work-related stress correlate with stress levels and whether it has a negative influence on health.Objectives: To investigate associations of the cynicism subscale scores of the Maslach Burnout Inventory-General Survey (MBI-GS) with levels of stress, anxiety, questionnaire-based physical health and with a number of physiological health risk indicators.Methods: Cynicism, anxiety, questionnaire-based physical health scores, as well as allostatic load, heart rate variability and C-reactive protein, were assessed in 27 males working between 40 and 80 irregular hours per week. Results:Cynicism scores related to stress levels (r=0.411, p=0.030). Effects of work-related cynicism on physical health were suggested by negative associations with questionnaire-based scores on physical health (r=-0.383, p=0.044) and heart rate variability indicators (r=-0.379, p=0.047 to r=-0.496, p=0.007), and by positive associations with anxiety levels (r=0.408, p=0.031), heart rate (r=0.449, p=0.017), BMI (r=0.426, p=0.024) allostatic load (r=0.360, p=0.065) and levels of the inflammatory marker C-reactive protein (r= 0.407, p=0.035).Conclusions: Cynicism, as reflected by the MBI-GS, increases with increases in stress levels and could contribute to the decline in the health reported for burnout.

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“…The measurement of fatigue using standard, validated instruments is common in many chronic illnesses, including cancer, chronic inflammatory diseases, depression, human immunodeficiency virus, and stroke, but generally not in GD [32][33][34]. The results of our literature review support fatigue as a core symptom in patients with Type 1 GD.…”

Section: Discussionmentioning

confidence: 59%