10 April 2020

Catecholamines induce long-lasting pro-inflammatory changes in monocytes in vitro and in vivo, indicating trained immunity. Charlotte van der Heijden and Niels Riksen, theme Vascular damage, and colleagues, contributed data to the understanding of pathways driving inflammatory changes in conditions characterized by high catecholamine levels, and propose that trained immunity underlies the increased cardiovascular event rate in PHEO patients. They have published their results in Circulation Research.

Exposure to high catecholamine levels is associated with inflammatory changes of myeloid cells and atherosclerosis, but the underlying mechanisms are only partly understood. To investigate whether the pro-inflammatory effects of noradrenaline and adrenaline can in part be explained by the induction of an immunological memory in innate immune cells, termed 'trained immunity'. 

In vitro, they exposed human primary monocytes to (nor)adrenaline for 24 hours, after which cells were rested and differentiated to macrophages over 5 days. After restimulation with LPS on day 6, (nor)adrenaline-exposed cells showed increased TNF-α production. This coincided with an increase in glycolysis and oxidative phosphorylation measured with Seahorse technology on day 6 before restimulation. Inhibition of the β-adrenoreceptor-cAMP signaling pathway prevented the induction of training. In vivo, they studied the functional, transcriptional, and epigenetic impact of peak-wise exposure to high catecholamine levels on monocytes isolated from pheochromocytoma/paraganglioma (PHEO) patients. In PHEO patients (n=10), the peripheral blood cell composition showed a myeloid bias and an increase of the inflammatory CD14+CD16++ intermediate monocyte subset compared to controls with essential hypertension (n=14). Ex vivo production of pro-inflammatory cytokines was higher in PHEO patients. These inflammatory changes persisted for 4 weeks after surgical removal of PHEO. Transcriptome analysis of circulating monocytes at baseline showed various differentially expressed genes in inflammatory pathways in PHEO patients; epigenetic profiling of the promoters of these genes suggestsenrichment of the transcriptionally-permissive chromatin mark H3K4me3, indicative of in vivo training.

Catecholamines induce long-lasting pro-inflammatory changes in monocytes in vitro and in vivo, indicating trained immunity. Their data contribute to the understanding of pathways driving inflammatory changes in conditions characterized by high catecholamine levels, and propose that trained immunity underlies the increased cardiovascular event rate in PHEO patients.

Related news items


Dutch Cancer Society Grant received by Annemiek van Spriel and Laia Querol-Cano

23 September 2020

Annemiek van Spriel and Laia Querol-Cano received a Dutch Cancer Society Grant of 707,298 euros to study the cancer cell surface in immunotherapy.

read more

Frank Walboomers 25-years work anniversary at Radboudumc

17 September 2020

Frank Walboomers, associate professor at the research group Regenerative Biomaterials at the Dept. of Dentistry (theme Reconstructive & Regenerative Medicine), celebrated his 25th work anniversary at Radboudumc.

read more

Tjitske Kleefstra appointed endowed professor of Clinical genetics and psychopathology of rare syndromes

17 September 2020

Tjitske Kleefstra has been appointed endowed professor of Clinical genetics and psychopathology of rare syndromes at the department of Neurodevelopmental disorders, with effect from 1 September.

read more

Annette Schenck appointed professor of Translational Genetics

17 September 2020

Annette Schenck has been appointed professor of Translational Genetics at the department of Neurodevelopmental disorders, with effect from 1 August. The chair will bring together fundamental and translational research in the field of brain developmental disorders.

read more

Centuries-old medicine reduces the risk of new cardiovascular disease in heart patients

17 September 2020

Colchicine, an anti-inflammatory drug that has been used for gout for centuries, has been shown to prevent cardiovascular disease in patients who have had a heart attack or are suffering from narrowed coronary arteries. Results of the study are published in the New England Journal of Medicine.

read more

Can a change in lifestyle relieve heart cramps?

10 September 2020

Cardiac spasm, or angina pectoris, is a common heart condition. Even though these patients are well monitored and treated, they are still at risk of more severe heart failure.

read more