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The β1-Adrenergic Receptor Contributes to Sepsis-Induced Immunosuppression Through Modulation of Regulatory T-Cell Inhibitory Function*

Durand, Manon; Hagimont, Eugenie; Louis, Huguette; Asfar, Pierre; Frippiat, Jean-Pol; Singer, Mervyn; Gauchotte, Guillaume; ... Kimmoun, Antoine; + view all (2022) The β1-Adrenergic Receptor Contributes to Sepsis-Induced Immunosuppression Through Modulation of Regulatory T-Cell Inhibitory Function*. Critical Care Medicine , 50 (9) E707-E718. 10.1097/CCM.0000000000005503. Green open access

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Abstract

OBJECTIVES: Although cardiovascular benefits of β1-adrenergic receptor blockade have been described in sepsis, little is known about its impact on the adaptive immune response, specifically CD4 T cells. Herein, we study the effects of β1-adrenergic receptor modulation on CD4 T-cell function in a murine model of sepsis. DESIGN: Experimental study. SETTING: University laboratory. SUBJECTS: C57BL/6 mice. INTERVENTIONS: High-grade sepsis was induced by cecal ligation and puncture in wild-type mice (β1+/+) with or without esmolol (a selective β1-adrenergic receptor blocker) or in β1-adrenergic receptor knockout mice (β1-/-). At 18 hours after surgery, echocardiography was performed with blood and spleen collected to analyze lymphocyte function. MEASUREMENTS AND MAIN RESULTS: At 18 hours, β1+/+cecal ligation and puncture mice exhibited characteristics of high-grade sepsis and three surrogate markers of immunosuppression, namely decreased splenic CD4 T cells, reduced CD4 T-cell proliferation, and increased regulatory T lymphocyte cell proportions. Pharmacologic and genetic β1-adrenergic receptor blockade reversed the impact of sepsis on CD4 T and regulatory T lymphocyte proportions and maintained CD4 T-cell proliferative capacity. β1-adrenergic receptor blocked cecal ligation and puncture mice also exhibited a global decrease in both pro- A nd anti-inflammatory mediators and improved in vivo cardiovascular efficiency with maintained cardiac power index despite the expected decrease in heart rate. CONCLUSIONS: β1-adrenergic receptor activation enhances regulatory T lymphocyte inhibitory function and thus contributes to sepsis-induced immunosuppression. This can be attenuated by β1-adrenergic receptor blockade, suggesting a potential immunoregulatory role for this therapy in the management of sepsis.

Type: Article
Title: The β1-Adrenergic Receptor Contributes to Sepsis-Induced Immunosuppression Through Modulation of Regulatory T-Cell Inhibitory Function*
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/CCM.0000000000005503
Publisher version: https://doi.org/10.1097/CCM.0000000000005503
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: adrenoreceptor, beta blocker, BETA(2)-ADRENERGIC RECEPTOR, BETA-BLOCKERS, BLOCKADE, Critical Care Medicine, CYTOKINE, ESMOLOL, EXPRESSION, General & Internal Medicine, HOST-RESISTANCE, immunosuppression, INFLAMMATION, Life Sciences & Biomedicine, lymphocytes, OUTCOMES, Science & Technology, sepsis, SEPTIC SHOCK
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10162762
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