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Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: Case control

Discussion in 'Latest ME/CFS Research' started by MeSci, Aug 6, 2017.

  1. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    Predictable...?

    Date: August 5, 2017
    URL: http://onlinelibrary.wiley.com/doi/10.1111/cei.13023/abstract

    Cytokine responses to exercise and activity in patients with
    chronic fatigue syndrome: Case control study
    ----------------------------------------------------------
    L.V. Clark(1), M. Buckland(2,*), G. Murphy(2), N. Taylor(2),
    V. Vleck(3), C. Mein(4), E. Wozniak(4), M. Smuk(1), P.D. White(1)
    1 Centre for Psychiatry, Wolfson Institute of Preventive Medicine,
    Queen Mary's School of Medicine and Dentistry, London, EC1M 6BQ.
    2 UCL Centre for Immunodeficiency, Royal Free London NHS
    Foundation Trust, London, WC1E 6BT.
    3 CIPER, Faculty of Human Kinetics, University of Lisbon, Estrada
    da Costa, Cruz Quebrada- Dafundo, 1499-002 Lisbon, Portugal.
    4 Genome Centre, Barts and the London School of Medicine and
    Dentistry, Queen Mary University of London, Charterhouse Square,
    London EC1M 6BQ.
    * Corresponding author: Dr Matthew Buckland.
    E-mail: mbuckland@nhs.net

    Summary

    Chronic fatigue syndrome (CFS) is characterized by fatigue after
    exertion. A systematic review suggested that transforming growth factor
    beta (TGF-beta) concentrations are often elevated in cases of CFS when
    compared to healthy controls. This study attempted to replicate this
    finding, and investigate whether post-exertional symptoms were
    associated with altered cytokine protein concentrations and their RNA in
    CFS patients.

    Twenty-four patients fulfilling Centers for Disease Control criteria for
    CFS, but with no comorbid psychiatric disorders, were recruited from two
    CFS clinics in London, UK. Twenty-one healthy, sedentary controls were
    matched by gender, age, and other variables. Circulating proteins and
    RNA were measured for TGF-beta, TNF, IL-8, IL-6 and IL-1beta. We
    measured six further cytokine protein concentrations (IL-2, IL-4, IL-5,
    IL-10, IL-12p70, and IFN-gamma). Measures were taken at rest, and before
    and after both commuting and aerobic exercise.

    CFS cases had higher TGF-beta protein levels compared to controls at
    rest (median (quartiles) = 43.9 (19.2, 61.8) versus 18.9 (16.1, 30.0)
    ng/ml) (p = 0.003), and consistently so over a nine-day period. However,
    this was a spurious finding due to variation between different assay
    batches.

    There were no differences between groups in changes to TGF-beta protein
    concentrations after either commuting or exercise. All other cytokine
    protein and RNA levels were similar between cases and controls.
    Post-exertional symptoms and perceived effort were not associated with
    any increased cytokines.

    We were unable to replicate previously found elevations in circulating
    cytokine concentrations, suggesting that elevated circulating cytokines
    are not important in the pathophysiology of CFS.

    --------
    (c) 2017 John Wiley & Sons, Inc.
     
  2. Cheshire

    Cheshire Senior Member

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  3. lilpink

    lilpink Senior Member

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    PDW really will stop at nothing to deny the biomedical basis of ME.


    This contradicts his own earlier findings (and indeed, a shed load of others’ findings of altered cytokines):


    Immunological changes after both exercise and activity in chronic fatigue syndrome: a pilot study. White PD, KE Nye, AJ Pinching et al. JCFS 2004:12 (2):51-66:


    “Immunological abnormalities are commonly observed in CFS…Concentrations of plasma transforming growth factor-beta (TGF-b) (anti-inflammatory) and tumour necrosis factor-alpha (TNF-a) (pro-inflammatory) have both been shown to be raised….Abnormal regulation of cytokines may both reflect and cause altered function across a broad range of cell types…..Altered cytokine levels, whatever their origin, could modify muscle and or neuronal function.

    Concentrations of TGF-b1 were significantly elevated in CFS patients at all times before and after exercise testing.


    “We found that exercise induced a sustained elevation in the concentration of TNF-a which was still present three days later, and this only occurred in the CFS patients.


    TGF-b was grossly elevated when compared to controls before exercise (and) showed an increase in response to the exercise entailed in getting to the study centre.


    “These data replicate three out of four previous studies finding elevated TGF-b in subjects with CFS.


    “The pro-inflammatory cytokine TNF-a is known to be a cause of acute sickness behaviour, characterised by reduced activity related to ‘weakness, malaise, listlessness and inability to concentrate’, symptoms also notable in CFS.


    “These preliminary data suggest that ‘ordinary’ activity (ie. that involved in getting up and travelling some distance) may induce anti-inflammatory cytokine release (TGFb), whereas more intense exercise may induce pro-inflammatory cytokine release (TNF-a) in patients with CFS”.
     
  4. hixxy

    hixxy Senior Member

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    @lilpin This paper is effectively a failed-replication of their own pilot study (the one you mentioned) so obviously they contradict each other. Not that I'm of fan of their work or anything ...
     
  5. BurnA

    BurnA Senior Member

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    What does that mean?
    How do they determine it was spurious I wonder?
     
  6. A.B.

    A.B. Senior Member

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  7. A.B.

    A.B. Senior Member

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    They wrote

     
    Dolphin, Esther12, MeSci and 3 others like this.
  8. notmyself

    notmyself Senior Member

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    there were other citokines studies a few days back,that contradict each other..i gues is a loose end
     
    Esther12 likes this.
  9. Cheshire

    Cheshire Senior Member

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    MeSci, Esther12 and Valentijn like this.
  10. msf

    msf Senior Member

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    I´m not normally a conspiracy person, but if you weren´t a complete moron (which the study´s authors may well be) and felt you needed to defend your career at any cost, wouldn´t you pick people who you suspected wouldn´t have been selected for studies such as Montoya´s for your own study? People with CFS rather than ME?
     
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  11. Sidereal

    Sidereal Senior Member

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    Or cytokines have nothing to do with ME symptoms and people need to move on from this and look elsewhere.
     
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  12. msf

    msf Senior Member

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    Yeh, it´s not that.
     
  13. msf

    msf Senior Member

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    To adapt something Christopher Hitchens once said: which is more likely, that Montoya´s, Lipkin´s and De Meirleir´s studies are wrong, or that White lied (or is a moron)?
     
    Last edited: Aug 6, 2017
    GreyOwl, Solstice, Jan and 4 others like this.
  14. msf

    msf Senior Member

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    Just wait for Hanson´s latest research, mentioned in Cort´s latest blog: ´Maureen Hanson, PhD - talk about an exciting project: last seen examining the effect exercise has on the immune system and metabolomics.´

    Basically, you´ve got all the smart people on one side, and all the dumb/amoral people on the other. Which side would you back? (I am talking about the ME field, and nothing else!)
     
  15. Murph

    Murph :)

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    This had the potential to be good science. I really like the way they took blood even before people got out of bed in the morning, just in case commuting to the hospital was the cause of higher cytokines. It could have validated the earlier cytokine finding, and kudos to these psychs for exploring a physical explanation.

    However, the principle of good scientific method is holding things constant and it seems they effed that up. The data are so wonky they can only assume one of their lab techs ran the centrifuge wrong. :(

    It's interesting to me that they still publish the study even after that. Good on the journal for accepting a null result I guess. I suppose it can serve as a warning on just how hard it is to do science well.

    Interestingly they even admit that the process error might have screwed up their initial TGF finding they were trying to replicate.

    "We cannot know whether the same laboratory variation explains the previous case control findings for TGF-, but case control studies can start subject recruitment with cases, in order to ascertain accurate matching of controls, so any inter-batch assay variation might explain why it appeared that cases had different concentrations from controls. We were unable to ascertain the differences in laboratory processing that led to the differences between batches, but assume that the difference was due to using different centrifuge times, which might affect TGF-release from platelets, leading to differences in TGF-concentrations."
     
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  16. msf

    msf Senior Member

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    It didn't really have the potential to be good science, as they just ignored the whole defining ME problem, thereby failing at the first hurdle.
     
  17. Valentijn

    Valentijn The Diabolic Logic

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    This sounds like suspicion of an artefact, with the source of the artefact not having been found. They imply human error, but give no details.

    They came from CFS clinics, which are generally avoided by ME patients and primarily recruit with Oxford. So I'd suspect they're on the lighter side of Fukuda, with no PEM being mandatory.

    TGF-B results seem pretty consistent thus far, which makes it a bit suspect that it was the positive result from this paper, and which they have then declared to be a false positive.
     
    Last edited: Aug 6, 2017
  18. Gijs

    Gijs Senior Member

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    Again an example of sloppy science. Using different centrifuges and blame it for inconsistenty makes this study useless. TGF B have been found many times before in CFS/ME patiënts. It could be an important finding. So, i like to see replication by other groups before we take any conclusion.
     
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  19. RogerBlack

    RogerBlack Senior Member

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    Would it not be usual practice to take enough blood to run the assays twice?
    So they can recover from oopses like this.
     
  20. A.B.

    A.B. Senior Member

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    Maybe it was the other centrifuge that malfunctioned because of a gremlin. After PACE I can't really trust these people anymore. Hiding a null result with clear harm to patients puts them into the lying scumbag category for me.
     

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