Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans

Matthijs Kox, Lucas T. van Eijk, Jelle Zwaag, Joanne van den Wildenberg, Fred C. G. J. Sweep, Johannes G. van der Hoeven, and Peter Pickkers
PNAS May 20, 2014 111 (20) 7379-7384; published ahead of print May 5, 2014 https://doi.org/10.1073/pnas.1322174111

  1. Edited by Tamas L. Horvath, Yale University School of Medicine, New Haven, CT, and accepted by the Editorial Board March 14, 2014 (received for review December 5, 2013)

Article Figures & SI

Figures

  • Fig. 1.
    Fig. 1.

    Cardiorespiratory parameters, temperature, and symptoms during experimental endotoxemia in control and trained subjects. (A) Carbon dioxide partial pressure (pCO2) in arterial blood. (B) Oxygen partial pressure (pO2) in arterial blood. (C) pH in arterial blood. (D) Bicarbonate (HCO3−) in arterial blood. (E) Lactate in arterial blood. (F) Oxygen saturation measured by pulse oximetry. (G) Heart rate (HR). (H) Mean arterial pressure (MAP). (I) Temperature. (J) Score of self-reported symptoms. Data are expressed as mean ± SEM of 12 subjects per group. Gray box indicates period in which the trained subjects practiced their learned breathing techniques. P values between groups were calculated using repeated measures two-way analysis of variance (ANOVA, interaction term). AU, arbitrary units; bpm, beats per minute.

  • Fig. 2.
    Fig. 2.

    Cardiorespiratory and biochemical changes during cyclic hyperventilation and breath retention in a representative subject of the trained group. (A) The respiratory rate alternately increased to around 20 breaths per minute (bpm) for several minutes, and then dropped to zero during voluntary breath retention. These cyclic changes in respiration resulted in profound changes in (B) oxygen saturation, (C) heart rate, and (D) mean arterial pressure. The data depicted were sampled from the monitor every 10 s. At the end of each hyperventilation phase and breath retention phase, an arterial blood sample was drawn for arterial blood gas analysis, of which the results are listed in the table below D. The cycles of hyper/hypoventilation in this particular subject can be viewed in Movie S2.

  • Fig. 3.
    Fig. 3.

    Plasma cathecholamine concentrations and serum cortisol concentrations during experimental endotoxemia in control and trained subjects. (A) Plasma epinephrine. (B) Plasma norepinephrine. (C) Plasma dopamine. (D) Serum cortisol. Data are expressed as mean ± SEM of 12 subjects per group. Gray box indicates period in which the trained subjects practiced their learned breathing techniques. P values between groups were calculated using repeated measures two-way analysis of variance (ANOVA, interaction term).

  • Fig. 4.
    Fig. 4.

    Plasma cytokine concentrations during endotoxemia in control and trained subjects. (A, C, E, and G) Median values of pro- (TNF-α, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines (n = 12 per group). (B, D, F, and H) Median ± interquartile range of area under curve (AUC) of pro- (TNF-α, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines (n = 12 per group; unit: ×104 pg/mL·h). P values were calculated using Mann–Whitney u tests.

  • Fig. 5.
    Fig. 5.

    Correlations in trained individuals. (A) Correlation between peak plasma levels of epinephrine (at T = 0 h) and plasma levels of the anti-inflammatory cytokine IL-10 at T = 1 h. (B) Correlation between plasma levels of the anti-inflammatory cytokine IL-10 at T = 1 h and peak plasma levels of the proinflammatory cytokine TNF-α (at T = 1.5 h). (C) Correlation between plasma levels of the anti-inflammatory cytokine IL-10 at T = 1 h and peak plasma levels of the proinflammatory cytokine IL-6 (at T = 2 h). (D) Correlation between plasma levels of the anti-inflammatory cytokine IL-10 at T = 1 h and peak plasma levels of the proinflammatory cytokine IL-8 (at T = 2 h). R and P values were calculated using Spearman correlation.

Tables

  • Table 1.

    Subject demographic characteristics

    ParameterTrained group, n = 12Control group, n = 12P value
    Age, y24 (19–27)22 (19–27)0.43
    Height, cm181 (172–190)185 (179–189)0.30
    Weight, kg75 (58–92)78 (65–91)0.25
    BMI, kg/m223 (19–26)23 (20–27)0.98
    HR, beats/min60 (41–80)61 (40–75)0.88
    MAP, mmHg92 (82–113)94 (78–105)0.89

    • Parameters were measured during screening visit. BMI, body mass index; HR, heart rate; MAP, mean arterial blood pressure. Data are presented as median (range). P values were calculated using Mann–Whitney u test.

Data supplements

  • Supporting Information

    Files in this Data Supplement:

    • Download Supporting Information (PDF)
    • Download Movie_S01 (AVI) - Movie S1. Impression of the training procedures in Poland. All subjects provided written consent.
    • Download Movie_S02 (AVI) - Movie S2. Practicing of breathing techniques (cyclic hyperventilation and breath retention) and cardiorespiratory and biochemical changes (text overlays) in a representative subject of the trained group during the endotoxemia experiment. The data in the text overlays were sampled from the monitor and from arterial blood gas analyses. Green, red, purple, and white text overlays indicate the parameters on the monitor. Data of this subject during the cycles of hyperventilation and breath retention shown in this video are also presented in Fig. 2. The subject provided written informed consent.
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Sympathetic nervous system limits immune response
Matthijs Kox, Lucas T. van Eijk, Jelle Zwaag, Joanne van den Wildenberg, Fred C. G. J. Sweep, Johannes G. van der Hoeven, Peter Pickkers
Proceedings of the National Academy of Sciences May 2014, 111 (20) 7379-7384; DOI: 10.1073/pnas.1322174111
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