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

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