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

  • David M. ShawEmail author
  • Fabrice Merien
  • Andrea Braakhuis
  • Lauren Keaney
  • Deborah K. Dulson
Original Article



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.


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.


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).


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.


Ketone supplement Nutritional ketosis Immune Lymphocyte Type-1/type-2 Interleukin Interferon 





Analysis of variance






Cluster of differentiation


Complementary deoxyribonucleic acid


Carbon dioxide




Effect size


Foetal bovine serum


Heart rate






Dipotassium ethylenediamine tetra-acetic acid


Ketone body




Messenger ribonucleic acid


Peripheral blood mononuclear cell


Phosphate-buffered saline




Reverse transcriptase polymerase chain reaction


Staphylococcal enterotoxin B








Upper respiratory tract symptom


Maximal oxygen uptake


Peak oxygen uptake


Second ventilatory threshold


Maximal wattage



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

Author 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.

Compliance with ethical standards

Conflict of interest

The authors do not have any conflicts of interest.

Supplementary material

421_2019_4263_MOESM1_ESM.docx (235 kb)
Supplementary file1 (DOCX 236 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Sports Performance Research Institute New Zealand (SPRINZ)Auckland University of TechnologyAucklandNew Zealand
  2. 2.AUT Roche Diagnostics Laboratory, School of ScienceAuckland University of TechnologyAucklandNew Zealand
  3. 3.Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand

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