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: 6.06). 06/2009; 266(2):196-206. DOI: 10.1111/j.1365-2796.2009.02079.x
Source: PubMed


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, Oct 06, 2015
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    • "The positive correlations between small Hsps and DJ-1 may be explained by increased ROS production. For example, in exercising muscles, increased levels of Hsp27 were associated with lower TBARS levels, suggesting that these Hsps may lower oxidative stress status [30]. In conclusion, increased ROS production may have induced simultaneously higher levels of DJ-1 and small Hsps. "
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    ABSTRACT: The development of proteomic biomarkers for meat tenderness remains an important challenge. The present study used Longissimus thoracis (LT) and Semitendinosus (ST) muscles of young bulls of three continental breeds (Aberdeen Angus, Blond d'Aquitaine and Limousin) to i) identify cellular pathways robustly related with meat tenderness, using potential protein biomarkers and ii) describe biochemical mechanisms underlying muscle to meat conversion. Correlation networks reveal robust correlations, i.e. present for at least two breeds, between potential meat tenderness biomarkers. For the two muscles of the three breeds, DJ-1 and Peroxiredoxin 6 were consistently correlated with Hsp20 and μ-calpain, respectively. For the three breeds, μ-calpain was related to Hsp70-8 in the LT muscle. Various correlations were muscle specific. For the three breeds, DJ-1 was correlated with Hsp27 for the ST, and with ENO3 and LDH-B for the LT muscle. Overall, in the LT, more correlations were found between proteins related to the glycolytic pathway and in the ST, with the small Hsps (Hsp20, 27 and αB-crystallin). Hsp70-Grp75 appeared involved in several relevant biological pathways. At the scientific level, results give insights in biological functions involved in meat tenderness. Further studies are needed to confirm the possible use of these biomarkers in the meat industry to improve assurance of good meat qualities.
    Journal of proteomics 09/2015; 128:365-374. DOI:10.1016/j.jprot.2015.08.022 · 3.89 Impact Factor
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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 · 5.89 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 · 3.53 Impact Factor
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