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

Durand, Manon; Hagimont, Eugénie; Louis, Huguette; Asfar, Pierre; Frippiat, Jean-Pol; Singer, Mervyn; Gauchotte, Guillaume; Labat, Carlos; Lacolley, Patrick; Lévy, Bruno; Chousterman, Benjamin; Kimmoun, Antoine

doi:10.1097/ccm.0000000000005503

Cited by 14 publications

(15 citation statements)

References 59 publications

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“…Basic differences in pathophysiology-hypothermia/ bradycardia versus fever/tachycardia-and differences in inflammatory gene expression have been mentioned. Indeed, the CLP-induced bradycardia documented by Durand et al (5) belies the statement that the model "depicts all hemodynamic … characteristics of a typical mid-grade sepsis. " Further, mice are more resistant to infection than humans.…”

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confidence: 88%

“…The findings of Durand et al (5) are also unique in their focus on β1ARs. Previous studies suggest that adrenergic effects on leukocytes to promote immunosuppression are β2AR-mediated (9).…”

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confidence: 89%

“…Perhaps the overzealous use of adrenergic agents represents an iatrogenic effect not unlike the use of large tidal-volume mechanical ventilation. Durand et al (5) and others suggest that β-adrenergic medications are immunosuppressive. These results suggest that reducing (or altogether avoiding) β-adrenergic agonists in septic patients is a strategy worthy of investigation.…”

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confidence: 99%

“…The article by Durand et al (5) in this issue of Critical Care Medicine exemplifies the need to present laboratory findings in a manner highlighting their clinical importance. The authors examined the effects of β-adrenergic blockade on CD4 + T cells using cell culture and mice subjected to cecal ligation and puncture (CLP), a frequently used procedure in rodents that mimics aspects of human sepsis.…”

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confidence: 99%

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Adrenergic Immune Effects: Is Beta the Enemy of Good?*

Deutschman¹,

Leisman

Taylor³

2022

Critical Care Medicine

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confidence: 88%

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confidence: 89%

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confidence: 99%

mentioning

confidence: 99%

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Adrenergic Immune Effects: Is Beta the Enemy of Good?*

Deutschman¹,

Leisman

Taylor³

2022

Critical Care Medicine

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“…The bene cial effects of Esmolol in septic shock were previously considered due to its hemodynamic effects [9]. However, recent evidence showed that the bene cial effects of Esmolol in septic shock were also associated with immunomodulation [10,11]. Whereas, how Esmolol in uencing immune response in septic shock and the optimal dose are unclear.…”

Section: Introductionmentioning

confidence: 99%

Low dose of Esmolol attenuates sepsis-induced immunosuppression via modulating T-lymphocyte apoptosis and differentiation

Cheng

Zheng

et al. 2022

Preprint

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Background Persistent immunosuppression characterized by immune cells apoptosis and T- lymphocyte subsets imbalance, occurs in septic patients with poor outcomes. Recent studies reported that Esmolol improved survival in septic shock via modulating immune responses. We hypothesized Esmolol alleviate sepsis-induced immunosuppression by regulating immune cell apoptosis and differentiation and sought to investigate the potential mechanisms and optimal dose. Methods Four hours after cecal ligation and puncture (CLP), Wistar rats were randomized into CLP, CLP + E-5 (Esmolol:5mg.kg− 1.h− 1) and CLP + E-18 (Esmolol:18mg.kg− 1.h− 1) group. Another 8 rats were under sham operation. 18 hours after CLP, hemodynamics and organ histological injuries were evaluated, peripheral blood mononuclear cells apoptosis and circulating T-lymphocyte subsets counts were determined by flow cytometry, protein expressions of p-Akt, Bcl-2, cleaved Caspase-3 and p-Erk1/2 were determined by western blot and immunohistochemistry. mRNA and protein expressions of β1-adrenoreceptors were evaluated by quantitative real-time PCR and immunohistochemistry. Results CLP induced tachycardia, hypotension, hyperlactatemia and multiple organ injuries. Infusion of Esmolol at 5mg.kg− 1.h− 1 didn't reduce heart rate, but improved mean arterial pressure, lactatemia and multiple organ injuries, decreased circulating T-lymphocyte apoptosis and the ratio of T help 2 cells and T help 1 cells, unregulated p-Akt and Bcl-2 expression and down-regulated cleaved Caspase-3 and p-Erk1/2 expression. Conclusions Esmolol without heart rate reduction attenuated sepsis-induced immunosuppression by preventing T-lymphocytes from apoptosis through regulating Akt/Bcl-2/Caspase-3 pathway and reducing naive CD4+ T cells differentiation to T help 2 cell through inhibiting Erk1/2 activation. Esmolol may be a potential immune regulator in septic shock.

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Alternatives to norepinephrine in septic shock: Which agents and when?

Jozwiak

2022

Journal of Intensive Medicine

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

Cited by 14 publications

References 59 publications

Adrenergic Immune Effects: Is Beta the Enemy of Good?*

Adrenergic Immune Effects: Is Beta the Enemy of Good?*

Low dose of Esmolol attenuates sepsis-induced immunosuppression via modulating T-lymphocyte apoptosis and differentiation

Alternatives to norepinephrine in septic shock: Which agents and when?

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