Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome

White, Andrea T.; Light, Alan R.; Hughen, Ronald W.; Bateman, Lucinda; Martins, Thomas B.; Hill, Harry R.; Light, Kathleen C.

doi:10.1111/j.1469-8986.2010.00978.x

Cited by 61 publications

(74 citation statements)

References 43 publications

(64 reference statements)

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“…Three studies recruited controls from the hospital setting, including outpatients (Jammes et al, 2009;Nas et al, 2011;Smylie et al, 2013). It was unclear whether control communities were the same as case communities in five studies (Bennett et al, 1997;Fletcher et al, 2009;Lloyd et al, 1994;Maes et al, 2012;Patarca et al, 1994) and there was no description of where controls were recruited from in 13 studies (Cannon et al, 1999;Cheney et al, 1989;Kennedy et al, 2004;Khaiboullina et al, 2014;Lattie et al, 2012;Linde et al, 1992;Nakamura et al, 2010;Nakatomi et al, 2014;Neu et al, 2014;Robinson et al, 2010;Scully et al, 2010;Straus et al, 1989;White et al, 2010). The definition of controls was the most poorly reported with only five studies explicitly stating that the controls had never had a history of CFS.…”

Section: Quality Assessmentmentioning

confidence: 94%

“…In 12 studies there was no matching of controls to cases (Buchwald et al, 1997;Garcia et al, 2014;Khaiboullina et al, 2014;Linde et al, 1992;Maes et al, 2013;Maes et al, 2012;Neu et al, 2014;Patarca et al, 1994;Smylie et al, 2013;Spence et al, 2008;White et al, 2010;Wyller et al, 2015). The factors that were matched including age, activity level, gender, body mass index, ethnicity, neighbourhood and menstrual cycle stage.…”

Section: Study Characteristicsmentioning

confidence: 96%

“…One of these studies required patients to fund their own tests (Maes et al, 2012). Seven papers did not state how patients were selected and therefore were unable to score positively for representation (Chao et al, 1991;Kennedy et al, 2004;Neu et al, 2014;Nijs et al, 2009;Patarca et al, 1994;Straus et al, 1989;White et al, 2010;White et al, 2004).…”

Section: Quality Assessmentmentioning

confidence: 97%

“…Six studies separated serum/plasma immediately, two studies within 30 minutes, five studies within 2 hours and one study within four hours (full details in table 6). Two studies flash/snap froze samples, which can considered the ideal method of sample handling (Nakamura et al, 2010;White et al, 2010).…”

Section: Sample Handlingmentioning

confidence: 99%

See 3 more Smart Citations

Chronic fatigue syndrome and circulating cytokines: A systematic review

Blundell

Ray

Buckland

et al. 2015

Brain, Behavior, and Immunity

125

143

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Section: Quality Assessmentmentioning

confidence: 94%

Section: Study Characteristicsmentioning

confidence: 96%

Section: Quality Assessmentmentioning

confidence: 97%

Section: Sample Handlingmentioning

confidence: 99%

See 2 more Smart Citations

Chronic fatigue syndrome and circulating cytokines: A systematic review

Blundell

Ray

Buckland

et al. 2015

Brain, Behavior, and Immunity

125

143

View full text Add to dashboard Cite

“…White et al (24) found differences between the patients and controls after stratifying the patients by whether they developed an exercise-induced symptom flare-up. Patients who developed symptom worsening 48 h after exercise showed increases in a number of cytokines, while those in whom symptoms did not worsen showed decreases in others.…”

Section: Discussionmentioning

confidence: 99%

Exercise and Sleep Deprivation Do Not Change Cytokine Expression Levels in Patients with Chronic Fatigue Syndrome

Nakamura

Schwander

Donnelly

et al. 2013

Clin Vaccine Immunol

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A major hypothesis regarding the cause of chronic fatigue syndrome (CFS) is immune dysregulation, thought to be reflected in upregulated proinflammatory cytokines leading to the symptoms that are characteristic of this illness. Because the symptoms worsen with physical exertion or sleep loss, we hypothesized that we could use these stressors to magnify the underlying potential pathogenic abnormalities in the cytokine systems of people with CFS. We conducted repeat blood sampling for cytokine levels from healthy subjects and CFS patients during both postexercise and total sleep deprivation nights and assayed for protein levels in the blood samples, mRNA activity in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs. We found that these environmental manipulations did not produce clinically significant upregulation of proinflammatory cytokines. These data do not support an important role of immune dysregulation in the genesis of stress-induced worsening of CFS. Chronic fatigue syndrome (CFS) is a medically unexplained illness characterized by new onset of fatigue that lasts for at least 6 months and is severe enough to produce a substantial decrease in physical activity. The fatigue must be accompanied by at least four of eight infectious, rheumatological, or neuropsychiatric symptoms (1). Because the illness onset is characterized as influenza-like in many patients, an early hypothesis that has continued to galvanize the research community is that CFS is caused by immune activation. That hypothesis was strengthened by an earlier report of high levels of immune activation markers in CFS (2). The hypothesis was further strengthened by the now-wellknown fact that the administration of proinflammatory cytokines produces sickness behaviors consisting of fever, severe fatigue, disturbed sleep, difficulty with cognitive processing, and musculoskeletal achiness (3), all of which are symptoms seen with CFS.We have spent considerable effort evaluating the hypothesis that CFS is caused by immune activation. In our initial study, we were unable to replicate the early finding of increased levels of immune activation markers in CFS (4). Subsequently, we reported that the levels of cytokine message (mRNA) were not different between CFS patients and matched controls and increased similarly for both groups after exhaustive exercise (5). In contrast to the hypothesis related to the upregulation of proinflammatory cytokines, we used advanced statistical modeling with neural networks and found evidence for increases in the daytime levels of interleukin 4 (IL-4), an anti-inflammatory Th2 cytokine (6).This finding led us to an alternative hypothesis. One of the most common complaints of both CFS and fibromyalgia (FM) patients is unrefreshing sleep. Cytokines are known to influence sleep, as proinflammatory cytokines increase sleep and anti-inflammatory cytokines interfere with sleep (7). We hypothesized that some patients with CFS have an unbalanced cytokine network with upregulated anti-inflammatory cyto...

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Are biomarkers associated with sensitivity to physical activity?

Flegg,

Lima,

Woznowski‐Vu

et al. 2023

European Journal of Pain

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BackgroundActivity‐based treatments play an integral role in managing musculoskeletal conditions including low back pain. However, while therapeutic exercise has been shown to reduce pain in such conditions, certain individuals experience a paradoxical pain increase in response to exercise. The physiological processes underlying this sensitivity to physical activity (SPA) are not fully understood, however stress and inflammation have been shown to contribute to SPA. The present cross‐sectional study investigated whether physiological indicators of stress (cortisol) and inflammation (IL‐6) help explain SPA.MethodsTwenty‐seven patients with chronic low back pain and 21 healthy controls completed a 1‐h exercise session of standardized physical tasks. SPA was calculated from the difference between post‐ and pre‐exercise pain levels. Participant's saliva was collected at several timepoints for cortisol and IL‐6 levels quantification. Their waking cortisol response was calculated to reflect their cortisol regulation. Reactivity of IL‐6 and cortisol was calculated to reflect changes in these measures during exercise.ResultsIL‐6 reactivity was significantly and positively correlated with SPA among participants with low back pain. In contrast, neither cortisol waking response nor cortisol reactivity was significantly correlated within the low back pain group. No significant differences in IL‐6 reactivity, cortisol reactivity or cortisol waking response were observed.ConclusionThese findings are the first to link SPA to an objective biomarker among people with low back pain. These findings help describe the physiological mechanisms of SPA and can support new clinical research that targets the inflammatory response of patients with chronic low‐back pain and elevated SPA.SignificanceThis study reveals a correlation between SPA and an objective salivary biomarker of IL‐6 in people with low back pain, improving our understanding of this clinically relevant subjective experience.

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Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome

Cited by 61 publications

References 43 publications

Chronic fatigue syndrome and circulating cytokines: A systematic review

Chronic fatigue syndrome and circulating cytokines: A systematic review

Exercise and Sleep Deprivation Do Not Change Cytokine Expression Levels in Patients with Chronic Fatigue Syndrome

Are biomarkers associated with sensitivity to physical activity?

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