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

Eur J Appl Physiol. 2020 Jan;120(1):191-202. doi: 10.1007/s00421-019-04263-x. Epub 2019 Nov 15.


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.

Keywords: Immune; Interferon; Interleukin; Ketone supplement; Lymphocyte; Nutritional ketosis; Type-1/type-2.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Butylene Glycols / pharmacology
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Enterotoxins / pharmacology
  • Humans
  • Ketosis / blood*
  • Ketosis / etiology
  • Male
  • Monocytes / metabolism
  • Physical Conditioning, Human / methods*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*


  • Butylene Glycols
  • Cytokines
  • Enterotoxins
  • enterotoxin B, staphylococcal
  • 1,3-butylene glycol