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Adrenergic Effect on Cytokine Release After Ex Vivo Healthy Volunteers’ Whole Blood LPS Stimulation

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Abstract

Catecholamines are molecules with immunomodulatory properties in health and disease. Several studies showed the effect of catecholamines when administered to restore hemodynamic stability in septic patients. This study investigates the effect of norepinephrine and dobutamine on whole blood cytokine release after ex vivo lipopolysaccharide (LPS) stimulation. Whole blood collected from healthy individuals was stimulated with LPS, in the presence of norepinephrine or dobutamine at different concentrations, with or without metoprolol, a β1 receptor antagonist. Cytokine measurement was performed in isolated cell culture supernatants with ELISA. Results are expressed as mean ± SEM and compared with Mann-Whitney rank-sum test. Both norepinephrine and dobutamine significantly reduced TNF-α and IL-6 production after ex vivo LPS stimulation of whole blood in a dose-dependent manner, and this effect was partially reversed by the presence of metoprolol. Norepinephrine and dobutamine reduce the LPS-induced production of pro-inflammatory cytokines, thus possibly contributing to altered balance between the inflammatory and anti-inflammatory responses, which are vital for a successful host response to severe disease, shock, and sepsis.

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Abbreviations

ELISA:

Enzyme-linked immunosorbent assay

ICU:

Intensive care unit

IL:

Interleukin

LPS:

Lipopolysaccharide

MODS:

Multiple organ dysfunction syndrome

NF-κB:

Nuclear factor-κB

PMA:

Phorbal-myristate-acetate

ROS:

Reactive oxygen species

SIRS:

Systemic inflammatory response syndrome

sTNFR:

Soluble TNF-α receptor

TNF-α:

Tumor necrosis factor-α

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Authors and Affiliations

  1. ICU Research Unit at “Agioi Anargyroi” General Hospital, National and Kapodistrian University of Athens, School of Health Sciences, Athens, Greece

    Vasiliki Papandreou, Nadia Kavrochorianou, Theodoros Katsoulas, Pavlos Myrianthefs, Kyriaki Venetsanou & George Baltopoulos

Authors
  1. Vasiliki Papandreou
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  2. Nadia Kavrochorianou
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  3. Theodoros Katsoulas
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  4. Pavlos Myrianthefs
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  5. Kyriaki Venetsanou
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  6. George Baltopoulos
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Corresponding author

Correspondence to Nadia Kavrochorianou.

Ethics declarations

This ex vivo study included healthy volunteers, who were not treated with any factor.

Informed Consent

All participants were informed about the aim and the expected results of this study, and written informed consent was obtained from all individual participants included in the study.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Papandreou, V., Kavrochorianou, N., Katsoulas, T. et al. Adrenergic Effect on Cytokine Release After Ex Vivo Healthy Volunteers’ Whole Blood LPS Stimulation. Inflammation 39, 1069–1075 (2016). https://doi.org/10.1007/s10753-016-0338-y

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