Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses

UMR MD2 (P2COE), Faculté de Médecine, Université de la Méditerranée, North Hospital, Assistance Publique - Hôpitaux de Marseille, France.
Journal of Internal Medicine (Impact Factor: 5.79). 06/2009; 266(2):196-206. DOI: 10.1111/j.1365-2796.2009.02079.x
Source: PubMed

ABSTRACT As heat shock proteins (Hsp) protect the cells against the deleterious effects of oxidative stress, we hypothesized that Hsp expression might be reduced in patients suffering from chronic fatigue syndrome (CFS) who present an accentuated exercise-induced oxidative stress.
This case-control study compared nine CFS patients to a gender-, age- and weight-matched control group of nine healthy sedentary subjects.
All subjects performed an incremental cycling exercise continued until exhaustion. We measured ventilation and respiratory gas exchange and evoked compound muscle potential (M-wave) recorded from vastus lateralis. Repetitive venous blood sampling allowed measurements of two markers of oxidative stress [thiobarbituric acid reactive substances (TBARS) and reduced ascorbic acid (RAA)], two cytokines (IL-6 and TNF-alpha) and two Hsp (Hsp27 and Hsp70) at rest, during maximal exercise and the 60-min recovery period.
Compared with controls, resting CFS patients had low baseline levels of RAA and Hsp70. Their response to maximal exercise associated (i) M-wave alterations indicating reduced muscle membrane excitability, (ii) early and accentuated TBARS increase accompanying reduced changes in RAA level, (iii) absence of significant increase in IL-6 and TNF-alpha, and (iv) delayed and marked reduction of Hsp27 and Hsp70 variations. The post-exercise increase in TBARS was accentuated in individuals having the lowest variations of Hsp27 and Hsp70.
The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress, which might result from delayed and insufficient Hsp production.

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Available from: Fabienne Bregeon, Aug 29, 2015
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    • "TGF-b IL-a, TNF, non-response rates. Failure to score this point was most commonly due to not stating how many of the cases and controls that were included in the study also had cytokine concentrations measured (Bennett et al., 1997; Cannon et al., 1999; Jammes et al., 2009; Kennedy et al., 2004; Lloyd et al., 1994; Nater et al., 2008; Spence et al., 2008; Swanink et al., 1996; Visser et al., 2001) or differences between the proportions of cases and controls who had their cytokine levels measured (compared to the total number included in the study) (Buchwald et al., 1997; Linde et al., 1992; Patarca et al., 1994). "
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    ABSTRACT: There has been much interest in the role of the immune system in the pathophysiology of chronic fatigue syndrome (CFS), as CFS may develop following an infection and cytokines are known to induce acute sickness behaviour, with similar symptoms to CFS. Using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a search was conducted on PubMed, Web of Science, Embase and PsycINFO, for CFS related-terms in combination with cytokine-related terms. Cases had to meet established criteria for CFS and be compared with healthy controls. Papers retrieved were assessed for both inclusionary criteria and quality. 38 papers met the inclusionary criteria. The quality of the studies varied. 77 serum or plasma cytokines were measured without immune stimulation. Cases of CFS had significantly elevated concentrations of Transforming Growth Factor-beta (TGF-) in five out of eight (63%) studies. No other cytokines were present in abnormal concentrations in the majority of studies, although insufficient data were available for some cytokines. Following physical exercise there were no differences in circulating cytokine levels between cases and controls and exercise made no difference to already elevated TGF-β concentrations. The finding of elevated TGF-β concentration, at biologically relevant levels, needs further exploration, but circulating cytokines do not seem to explain the core characteristic of post-exertional fatigue. Copyright © 2015. Published by Elsevier Inc.
    Brain Behavior and Immunity 07/2015; DOI:10.1016/j.bbi.2015.07.004 · 6.13 Impact Factor
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    • "Loss of energy/weakness Cardiopulmonary exercise test (CPET) (American College of Sports Medicine, 2009; Balady et al., 2010) De Becker et al., 2000; Farquhar et al., 2002; Jones et al., 2012 Cognitive deficits Specific neurocognitive tests* (Wechsler, 1981; Cambridge Cognition, 1999; Lezak et al., 2004; Strauss et al., 2006) DeLuca et al., 1993, 2004; Tiersky et al., 1997; Dickson et al., 2009; Thomas and Smith, 2009; Cockshell and Mathias, 2010; Constant et al., 2011 Muscle weakness Muscle (power and endurance) tests (Van der Ploeg, 1991; Andrews et al., 1996; Wang et al., 2002; Stark et al., 2011) Paul et al., 1999; Fulcher and White, 2000; Lawrie et al., 2000; Siemionow et al., 2004 Orthostatic intolerance Tilt table test (Streeten, 1987; American College of Cardiology et al., 1996; Task Force for the Diagnosis and Management of Syncope, 2009) Rowe et al., 1995; De Lorenzo et al., 1997; Streeten and Anderson, 1998; Stewart et al., 1999; Newton et al., 2007; Galland et al., 2008; Hoad et al., 2008; Katz et al., 2011 Post-exertional malaise Physical Repeated cardiopulmonary exercise tests, 24 h apart (Katch et al., 1982; Amann et al., 2004; Bensimhon et al., 2008; Balady et al., 2010) VanNess et al., 2006; Patrick Neary et al., 2008; Vermeulen et al., 2010; Snell et al., 2013 Cognitive Specific neurocognitive tests* (Wechsler, 1981; Cambridge Cognition, 1999; Lezak et al., 2004; Strauss et al., 2006), before and after a CPET or orthostatic stress VanNess et al., 2007; Ocon et al., 2012 Visual symptoms Useful field of view tests (Ball et al., 1993; Ball and Owsley, 1993) and eye movement tests (Rommelse et al., 2008) Leslie, 1997; Vedelago, 1997; Badham and Hutchinson, 2013; Hutchinson and Badham, 2013 Sleep disturbances Polysomnografic investigation (Rechtschaffen and Kales, 1968; Dumermuth et al., 1983; Lo et al., 2002; Iber et al., 2007) Kishi et al., 2008, 2011; Decker et al., 2009 Defective stress response Hormonal investigation (Kirschbaum et al., 1993; Holtorf, 2008; Kovacs and Ojeda, 2011; Melmed et al., 2011) MacHale et al., 1998; Gaab et al., 2002; Cleare, 2004; Jerjes et al., 2005; Holtorf, 2008; Torres-Harding et al., 2008; Jammes et al., 2009; Papadopoulos and Cleare, 2011; Tak et al., 2011 *Cognitive impairments can be identified if appropriate measures/tests are used (Thomas and Smith, 2009; Cockshell and Mathias, 2010). immunological abnormalities. "
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    ABSTRACT: Myalgic Encephalomyelitis (ME) was identified as a new clinical entity in 1959 and has been acknowledged as a disease of the central nervous system/neurological disease by the World Health Organisation since 1969. Cognitive impairment, (muscle) weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after minor exertion, are distinctive symptoms of ME.Chronic Fatigue Syndrome (CFS) was introduced in 1988 and was redefined into clinically evaluated, unexplained (persistent or relapsing) chronic fatigue, accompanied by at least four out of a list of eight symptoms, e.g. headaches and unrefreshing sleep, in 1994.Although the labels are used interchangeably, ME and CFS define distinct diagnostic entities. Post-exertional malaise and cognitive deficits e.g. are not mandatory for the diagnosis CFS, while obligatory for the diagnosis ME. “Fatigue” is not obligatory for the diagnosis ME.Since fatigue and other symptoms are subjective and ambiguous, research has been hampered. Despite this and other methodological issues, research has observed specific abnormalities in ME/CFS repetitively, e.g. immunological abnormalities, oxidative and nitrosative
    Frontiers in Physiology 03/2014; 5:109. DOI:10.3389/fphys.2014.00109 · 3.50 Impact Factor
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    • "Symptom exacerbation (i.e., PEM) related to even mild exercise has been reported to occur in greater than 95% of CFS patients.[2] In the literature, the patient reactions associated with PEM have included increased symptoms of pain and fatigue,[3] [4] [5] abnormal cardiopulmonary responses to exercise,[2] [6] [7] decreases in physical activity behaviors,[4] [8] [9] changes in cognitive function,[10] [11] and up-regulation of numerous biological variables.[12] [13] Although a number of studies have been conducted, consistent results and/or replication of findings have been rare.[14] "
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    ABSTRACT: Background: A primary complaint of chronic fatigue syndrome (CFS) patients is post-exertion malaise, which is a worsening of symptoms following activities such as exercise. Purpose: To examine the link between gene expression for metabolite, adrenergic, immune, and glucocorticoid receptors on leukocytes and symptoms (pain, fatigue, and mood) following a maximal exercise test. Methods: Thirteen CFS patients and 11 healthy participants matched on age and fitness underwent blood draws and completed questionnaires immediately before, and 15 minutes, 48 hours, and 72 hours following, maximal exercise. Symptom and genetic measures collected before and after exercise were compared using a doubly multivariate repeated-measures analysis of variance. Results: This comparison of CFS and healthy participants resulted in a significant multivariate main effect for Group (p textless 0.05). Univariate analyses indicated group differences for adrenergic α-2A and glucocorticoid (NR3C1) receptor messenger ribonucleic acid and symptoms of fatigue and confusion. Changes in gene expression were significantly correlated with symptoms. Conclusions: Results suggest that increased glucocorticoid sensitivity may contribute to the symptoms of post-exertion malaise in CFS. As NR3C1 interacts with other transcription factors, investigating the resulting cascades may lead to greater understanding of the biological mechanism of post-exertion malaise. This finding, if confirmed, could lead to novel approaches to prevent symptom exacerbation in CFS.
    10/2013; 1(4):190-209. DOI:10.1080/21641846.2013.838444
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