Research Papers: Immunology:

Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity

Bernhard F. Gibbs, Isabel Gonçalves Silva, Alexandr Prokhorov, Maryam Abooali, Inna Yasinska, Maxwell A. Casely-Hayford, Steffen M. Berger, Elizaveta Fasler-Kan and Vadim Sumbayev _

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Oncotarget. 2015; 6:28678-28692. https://doi.org/10.18632/oncotarget.5212

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Bernhard F. Gibbs1,*, Isabel Gonçalves Silva1,*, Alexandr Prokhorov1,*, Maryam Abooali1, Inna M. Yasinska1, Maxwell A. Casely-Hayford1, Steffen M. Berger2, Elizaveta Fasler-Kan2,3, Vadim V. Sumbayev1

1School of Pharmacy, University of Kent, Chatham Maritime, ME4 4TB Kent, United Kingdom

2Department of Pediatric Surgery and Department of Clinical Research, Inselspital, University Hospital, University of Bern, CH-3010 Bern, Switzerland

3Department of Biomedicine, University of Basel and University Hospital Basel, CH-4031 Basel, Switzerland

*These authors have contributed equally to this work

Correspondence to:

Vadim Sumbayev, e-mail: [email protected]

Elizaveta Fasler-Kan, e-mail: [email protected]

Keywords: myeloid cells, caffeine, Inflammation, allergy

Received: July 06, 2015     Accepted: August 31, 2015     Published: September 11, 2015


Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have previously been ascribed largely to its inhibitory actions on phosphodiesterase. However, more recent studies suggest an additional role in affecting the activity of the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways, although detailed molecular events underlying its mode of action have not been elucidated. Here, we report the cellular uptake of caffeine, without metabolisation, by healthy and malignant hematopoietic myeloid cells including monocytes, basophils and primary acute myeloid leukaemia mononuclear blasts. Unmodified caffeine downregulated mTOR signalling, which affected glycolysis and the release of pro-inflammatory/pro-angiogenic cytokines as well as other inflammatory mediators. In monocytes, the effects of caffeine were potentiated by its ability to inhibit xanthine oxidase, an enzyme which plays a central role in human purine catabolism by generating uric acid. In basophils, caffeine also increased intracellular cyclic adenosine monophosphate (cAMP) levels which further enhanced its inhibitory action on mTOR. These results demonstrate an important mode of pharmacological action of caffeine with potentially wide-ranging therapeutic impact for treating non-infectious disorders of the human immune system, where it could be applied directly to inflammatory cells.

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