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Clinical Immunology

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

Toru Nakamura, Stephan Schwander, Robert Donnelly, Dane B. Cook, Felix Ortega, Fumiharu Togo, Yoshiharu Yamamoto, Neil S. Cherniack, Marc Klapholz, David Rapoport, Benjamin H. Natelson
Toru Nakamura
aPain & Fatigue Study Center, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA
bDepartment of Neurosciences, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA
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Stephan Schwander
cDepartment of Medicine, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA
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Robert Donnelly
cDepartment of Medicine, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA
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Dane B. Cook
dDepartment of Kinesiology, University of Wisconsin School of Education, Madison, Wisconsin, USA
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Felix Ortega
cDepartment of Medicine, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA
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Fumiharu Togo
eEducational Physiology Laboratory, Graduate School of Education, The University of Tokyo, Tokyo, Japan
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Yoshiharu Yamamoto
eEducational Physiology Laboratory, Graduate School of Education, The University of Tokyo, Tokyo, Japan
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Neil S. Cherniack
aPain & Fatigue Study Center, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA
cDepartment of Medicine, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA
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Marc Klapholz
cDepartment of Medicine, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA
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David Rapoport
fDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, NYU School of Medicine, New York, New York, USA
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Benjamin H. Natelson
aPain & Fatigue Study Center, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA
bDepartment of Neurosciences, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA
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DOI: 10.1128/CVI.00527-13
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    Fig 1

    Schematic showing flow of studies. Analysis of data following exercise or during sleep deprivation was done using data from subjects who had already provided data on the normal night.

  • Fig 2
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    Fig 2

    Group-averaged IL-1β in the stimulated condition (the number of producing cells) from ELISPOT assay for the control and CFS-only groups during the postexercise night. The error bars indicate the standard error of the means. *, significant difference from control; note that the statistical tests were conducted with log-transformed data.

Tables

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  • Table 1

    Significant effects of sleep deprivation on cytokine levels measured by three different assays

    Assay type and cytokine testedData for each groupa
    ControlCFS
    NormalSleep deprivationNormalSleep deprivation
    ELISPOT assay (n)1213
        IL-1βb94.2 ± 70.0140.1 ± 94.125.7 ± 13.140.7 ± 13.2e
        IL-8b37.2 ± 11.556.1 ± 16.3e60.1 ± 12.269.8 ± 11.7
    Luminex assay (n)910
        IL-1βc0.03 ± 0.020.08 ± 0.04e0.18 ± 0.070.14 ± 0.05
    qRT-PCR assay (n)1315
        IL-4d0.76 ± 0.330.29 ± 0.11e0.42 ± 0.131.34 ± 0.92
        IL-10d0.55 ± 0.150.50 ± 0.180.36 ± 0.060.25 ± 0.03e
    • ↵a The statistical tests were conducted with log-transformed data. Values in bold type indicate significant cases.

    • ↵b No. of cytokine-producing cells (mean ± SE) (raw data).

    • ↵c Cytokine level (mean ± SE) (pg/ml) (raw data).

    • ↵d Cytokine level (relative quantity) (mean ± SE) (raw data).

    • ↵e Significant within-group difference from normal night.

  • Table 2

    Significant effects of exercise stress on cytokine levels measured by three different assays

    Assay type and cytokine testedaData for each groupb
    ControlCFSCFS onlyCFS+FM
    NormalExerciseNormalExerciseNormalExerciseNormalExercise
    ELISPOT assay171596
        IL-1βc74.4 ± 50.2109.9 ± 62.6f28.4 ± 11.926.4 ± 8.037.3 ± 18.329.0 ± 10.715.0 ± 8.922.5 ± 12.0
        IL-4c6.9 ± 1.58.4 ± 2.611.6 ± 2.47.7 ± 1.8f12.5 ± 2.97.4 ± 2.4f10.2 ± 4.18.2 ± 2.7
        IL-6c47.2 ± 11.469.2 ± 16.274.7 ± 21.751.0 ± 20.4f50.9 ± 18.28.1 ± 3.2f110.0 ± 43.0115.2 ± 38.0g
        ST IL-6c96.8 ± 14.1117.2 ± 16.3118.5 ± 16.795.1 ± 16.7f108.4 ± 11.867.9 ± 16.9f134.0 ± 36.6135.7 ± 25.5
        IL-8c36.2 ± 8.554.9 ± 13.657.8 ± 10.124.6 ± 5.4f58.9 ± 14.025.8 ± 5.956.1 ± 13.922.8 ± 10.2f
        ST IL-8c50.1 ± 10.062.9 ± 13.572.2 ± 7.832.0 ± 7.5f60.6 ± 11.131.4 ± 10.0f89.0 ± 6.433.0 ± 11.1f
        TNF-αc145.1 ± 28.0182.6 ± 30.3f130.0 ± 33.4151.3 ± 22.5f157.6 ± 46.5148.7 ± 27.388.6 ± 40.7155.0 ± 38.6f
    Luminex assay171596
        IL-1βd0.09 ± 0.040.11 ± 0.050.33 ± 0.110.34 ± 0.120.16 ± 0.070.16 ± 0.070.57 ± 0.22h0.60 ± 0.25
        IL-4d0.18 ± 0.080.10 ± 0.03f0.07 ± 0.030.06 ± 0.020.02 ± 0.020.06 ± 0.030.15 ± 0.070.08 ± 0.05
        IL-10d2.22 ± 0.391.40 ± 0.25f2.37 ± 0.342.24 ± 0.342.02 ± 0.432.07 ± 0.492.89 ± 0.542.49 ± 0.37
    qRT-PCR assay (n)e1817107
    • ↵a ST, stimulant-induced data.

    • ↵b The statistical tests were conducted with log-transformed data. Values in bold type indicate significant cases.

    • ↵c No. of cytokine-producing cells (mean ± SE) (raw data).

    • ↵d Cytokine level (mean ± SE) (pg/ml) (raw data).

    • ↵e There were no significant cases for the qRT-PCR assay.

    • ↵f Significant within-group difference from normal night.

    • ↵g Significant difference between CFS only and CFS+FM.

    • ↵h Significant difference between control subjects and patients with CFS+FM.

  • Table 3

    VAS scores before and after sleep deprivation and exercise nights

    Type of night and groupVAS scores (mean ± SD) by categorya
    SleepinessPainFeeling blueAnxietyFatigue
    Normal night
        Control
            Before sleep4.7 ± 4.00.1 ± 0.20.2 ± 0.71.7 ± 3.63.1 ± 4.2
            After awake2.5 ± 3.1c0.3 ± 0.80.3 ± 0.80.7 ± 1.31.4 ± 2.1c
        CFS
            Before sleep8.8 ± 4.0b7.1 ± 3.9b1.1 ± 1.9b1.5 ± 2.09.4 ± 3.0b
            After awake7.8 ± 3.6b7.1 ± 3.8b0.9 ± 1.60.9 ± 1.78.2 ± 3.2b
    Night of sleep deprivation
        Control
            Before deprivation3.6 ± 5.30.9 ± 2.10.1 ± 0.20.8 ± 1.72.2 ± 4.6
            After deprivation4.7 ± 4.50.9 ± 1.80.2 ± 0.50.2 ± 0.53.5 ± 4.5
        CFS
            Before deprivation9.6 ± 3.7b8.3 ± 2.6b0.9 ± 1.2b0.9 ± 1.110.5 ± 2.7b
            After deprivation11.2 ± 4.4b9.8 ± 3.4b,c0.6 ± 0.90.9 ± 0.9b11.9 ± 3.2b,c
    Night following exercise
        Control
            Before sleep3.7 ± 3.60.0 ± 0.00.04 ± 0.140.7 ± 1.82.4 ± 3.6
            After awake1.2 ± 1.40.0 ± 0.00.1 ± 0.20.05 ± 0.170.6 ± 1.3
        CFS
            Before sleep10.4 ± 3.8b8.7 ± 4.5b1.0 ± 1.4b1.8 ± 3.010.5 ± 3.4b
            After awake8.3 ± 4.0b8.1 ± 5.2b0.5 ± 0.8b,c0.7 ± 1.0b9.5 ± 3.7b
    • ↵a Values in boldface indicate the cases where the experimental effects on subjective symptoms were significant (repeated-ANOVA, P < 0.05; Bonferroni multiple comparison adjustment was used).

    • ↵b Significant difference from healthy controls.

    • ↵c Significant difference between before and after sleep deprivation/exercise tests.

Additional Files

  • Figures
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  • Supplemental material

    Files in this Data Supplement:

    • Supplemental file 1 -

      Supplemental statistical models. Specification of multilevel models. Table S1. Effects of sleep deprivation on cytokine protein production levels measured by an ELISPOT assay. Table S2. Effects of sleep deprivation on cytokine protein production levels measured on a Luminex assay. Table S3. Effects of sleep deprivation on cytokine mRNA expression levels measured by a qRT-PCR assay. Table S4. Effects of exercise stress on cytokine production levels measured by an ELISPOT assay. Table S5. Effects of exercise stress on cytokine protein production levels measured by a Luminex assay. Table S6. Effects of exercise stress on cytokine mRNA expression levels measured by a qRT-PCR assay.

      PDF, 199K

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Exercise and Sleep Deprivation Do Not Change Cytokine Expression Levels in Patients with Chronic Fatigue Syndrome
Toru Nakamura, Stephan Schwander, Robert Donnelly, Dane B. Cook, Felix Ortega, Fumiharu Togo, Yoshiharu Yamamoto, Neil S. Cherniack, Marc Klapholz, David Rapoport, Benjamin H. Natelson
Clinical and Vaccine Immunology Oct 2013, 20 (11) 1736-1742; DOI: 10.1128/CVI.00527-13

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Exercise and Sleep Deprivation Do Not Change Cytokine Expression Levels in Patients with Chronic Fatigue Syndrome
Toru Nakamura, Stephan Schwander, Robert Donnelly, Dane B. Cook, Felix Ortega, Fumiharu Togo, Yoshiharu Yamamoto, Neil S. Cherniack, Marc Klapholz, David Rapoport, Benjamin H. Natelson
Clinical and Vaccine Immunology Oct 2013, 20 (11) 1736-1742; DOI: 10.1128/CVI.00527-13
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