Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis

PLoS One. 2017 Jul 24;12(7):e0180900. doi: 10.1371/journal.pone.0180900. eCollection 2017.


A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR)-activation and glucose-deprivation or co-treatment with 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG) increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Bacterial Load
  • Cells, Cultured
  • Deoxyglucose / pharmacology
  • Disease Models, Animal
  • Fasting / metabolism*
  • Female
  • Humans
  • Interleukin-10 / metabolism*
  • Interleukin-12 / metabolism*
  • Listeriosis / immunology
  • Listeriosis / metabolism
  • Listeriosis / microbiology
  • Metabolome
  • Mice
  • Mice, Inbred BALB C
  • Myeloid Cells / drug effects
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Toll-Like Receptors / metabolism


  • Toll-Like Receptors
  • Interleukin-10
  • Interleukin-12
  • Deoxyglucose
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases