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Involvement of beta1-adrenergic modulation on lymphocyte balance during experimental septic shock

Abstract : Rationale: Sepsis typically induces dysautonomia, an over-activation of the sympathetic nervous system. This can lead to impaired cardiovascular function and immunosuppression, both of which are associated with poor outcome. Beta1-adrenoreceptor blockade downregulates dysautonomia. Although cardiovascular benefits of β1-adrenoreceptor blockade have been described in sepsis, little is known about its impact on the adaptive immune response, specifically CD4 T cells. Objective: To investigate the effects of β1-adrenoreceptor modulation on CD4 T cell function in a murine model of sepsis. Methods and results: High-grade sepsis was induced by caecal ligation and puncture (CLP) in wild-type mice (1+/+) with or without esmolol (a selective β1-adrenoreceptor blocker), or in β1-adrenoreceptor knockout mice (1-/-). At 18 hours, 1+/+ 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 Treg cell proportions. Pharmacologic and genetic β1-adrenoreceptor blockade reversed the impact of sepsis on CD4 and Treg proportions and maintained CD4 T cell proliferative capacity. β1-adrenoreceptor blocked mice also exhibited a global decrease in both pro- and anti-inflammatory mediators and improved in-vivo cardiovascular efficiency with a maintained cardiac power index despite the expected decrease in heart rate. Conclusion: β1-adrenoreceptor activation enhances Treg inhibitory function and thus contributes to sepsis-induced immunosuppression. This can be attenuated by β1-adrenoreceptor blockade, suggesting a potential immunoregulatory role for this therapy in the treatment of sepsis.
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https://hal.univ-lorraine.fr/tel-03284816
Contributor : Thèses Ul <>
Submitted on : Monday, July 12, 2021 - 9:01:18 PM
Last modification on : Thursday, July 29, 2021 - 2:19:24 PM

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  • HAL Id : tel-03284816, version 1

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Manon Durand. Involvement of beta1-adrenergic modulation on lymphocyte balance during experimental septic shock. Immunology. Université de Lorraine, 2021. English. ⟨NNT : 2021LORR0024⟩. ⟨tel-03284816⟩

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