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Acute hyperketonaemia alters T-cell-related cytokine gene expression within stimulated peripheral blood mononuclear cells following prolonged exercise

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European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Purpose

We investigated the effect of the racemic β-hydroxybutyrate precursor, R,S-1,3-butanediol (BD), on T-cell-related cytokine gene expression within stimulated peripheral blood mononuclear cells (PBMC) following prolonged, strenuous exercise.

Methods

A repeated-measures, randomised, crossover study was conducted in nine healthy, trained male cyclists (age, 26.7 ± 5.2 years; VO2peak, 63.9 ± 2.5 mL kg−1 min−1). Participants ingested 0.35 g kg−1 of BD or placebo 30 min before and 60 min during 85 min of steady-state (SS) exercise, which preceded a ~ 30 min time-trial (TT) (7 kJ kg−1). Blood samples were collected at pre-supplement, pre-exercise, post-SS, post-TT and 1-h post-TT. Whole blood cultures were stimulated with Staphylococcal enterotoxin B (SEB) for 24 h to determine T-cell-related interleukin (IL)-4, IL-10 and interferon (IFN)-γ mRNA expression within isolated PBMCs in vitro.

Results

Serum cortisol, total circulating leukocyte and lymphocyte, and T-cell subset concentrations were similar between trials during exercise and recovery (all p > 0.05). BD ingestion increased T-cell-related IFN-γ mRNA expression compared with placebo throughout exercise and recovery (p = 0.011); however, IL-4 and IL-10 mRNA expression and the IFN-γ/IL-4 mRNA expression ratio were unaltered (all p > 0.05).

Conclusion

Acute hyperketonaemia appears to transiently amplify the initiation of the pro-inflammatory T-cell-related IFN-γ response to an immune challenge in vitro during and following prolonged, strenuous exercise; suggesting enhanced type-1 T-cell immunity at the gene level.

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Abbreviations

AcAc:

Acetoacetate

ANOVA:

Analysis of variance

β2-MG:

β2-Microglobulin

BD:

R,S-1,3-Butanediol

CD:

Cluster of differentiation

cDNA:

Complementary deoxyribonucleic acid

CO2 :

Carbon dioxide

D-βHB:

D-beta-hydroxybutyrate

ES:

Effect size

FBS:

Foetal bovine serum

HR:

Heart rate

IFN:

Interferon

IL:

Interleukin

K2EDTA:

Dipotassium ethylenediamine tetra-acetic acid

KB:

Ketone body

kJ:

Kilojoules

mRNA:

Messenger ribonucleic acid

PBMC:

Peripheral blood mononuclear cell

PBS:

Phosphate-buffered saline

PLA:

Placebo

RT-PCR:

Reverse transcriptase polymerase chain reaction

SEB:

Staphylococcal enterotoxin B

SS:

Steady-state

T-cell:

T-lymphocyte

TT:

Time-trial

URTS:

Upper respiratory tract symptom

VO2max :

Maximal oxygen uptake

VO2peak :

Peak oxygen uptake

VT2 :

Second ventilatory threshold

W max :

Maximal wattage

References

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Acknowledgements

The authors would like to thank the participants for their effort, cooperation and humour.

Author information

Authors and Affiliations

Authors

Contributions

The study was designed by DS, FM, AB and DD; data were collected by DS; data interpretation and manuscript preparation were undertaken by DS, FM, AB, LK and DD. All authors approved the final version of the paper.

Corresponding author

Correspondence to David M. Shaw.

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Conflict of interest

The authors do not have any conflicts of interest.

Additional information

Communicated by Klaas R. Westerterp.

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Cite this article

Shaw, D.M., Merien, F., Braakhuis, A. et al. Acute hyperketonaemia alters T-cell-related cytokine gene expression within stimulated peripheral blood mononuclear cells following prolonged exercise. Eur J Appl Physiol 120, 191–202 (2020). https://doi.org/10.1007/s00421-019-04263-x

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  • DOI: https://doi.org/10.1007/s00421-019-04263-x

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