• Critical care medicine · Sep 2022

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

    • Manon Durand, Eugénie Hagimont, Huguette Louis, Pierre Asfar, Jean-Pol Frippiat, Mervyn Singer, Guillaume Gauchotte, Carlos Labat, Patrick Lacolley, Bruno Levy, Glenn ChoustermanBenjaminBDépartement d'Anesthésie-Réanimation, Université de Paris, APHP, CHU Lariboisière, FHU PROMICE, Inserm U942, Paris, France.F-CRIN-INI-CRCT, Vandœuvre-lès-Nancy, France., and Antoine Kimmoun.
    • Université de Lorraine, Inserm U1116, DCAC, Nancy, France.
    • Crit. Care Med. 2022 Sep 1; 50 (9): e707-e718.

    ObjectivesAlthough cardiovascular benefits of β 1 -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 β 1 -adrenergic receptor modulation on CD4 T-cell function in a murine model of sepsis.DesignExperimental study.SettingUniversity laboratory.SubjectsC57BL/6 mice.InterventionsHigh-grade sepsis was induced by cecal ligation and puncture in wild-type mice (β 1+/+ ) with or without esmolol (a selective β 1 -adrenergic receptor blocker) or in β 1 -adrenergic receptor knockout mice (β 1-/- ). At 18 hours after surgery, echocardiography was performed with blood and spleen collected to analyze lymphocyte function.Measurements And Main ResultsAt 18 hours, β 1+/+ 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 β 1 -adrenergic receptor blockade reversed the impact of sepsis on CD4 T and regulatory T lymphocyte proportions and maintained CD4 T-cell proliferative capacity. β 1 -adrenergic receptor blocked cecal ligation and puncture mice also exhibited a global decrease in both pro- and anti-inflammatory mediators and improved in vivo cardiovascular efficiency with maintained cardiac power index despite the expected decrease in heart rate.Conclusionsβ 1 -adrenergic receptor activation enhances regulatory T lymphocyte inhibitory function and thus contributes to sepsis-induced immunosuppression. This can be attenuated by β 1 -adrenergic receptor blockade, suggesting a potential immunoregulatory role for this therapy in the management of sepsis.Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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