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- and 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.

中文翻译：

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β1-肾上腺素受体通过调节调节性 T 细胞抑制功能有助于脓毒症诱导的免疫抑制*

目标： 

_{尽管 β 1-}肾上腺素受体阻断剂对心血管的益处已在脓毒症中得到描述，但对其对适应性免疫反应，特别是 CD4 T 细胞的影响知之甚少。在此，我们研究了 β _1-肾上腺素能受体调节对脓毒症小鼠模型中 CD4 T 细胞功能的影响。

设计： 

实验研究。

环境： 

大学实验室。

主题： 

C57BL/6 小鼠。

干预： 

野生型小鼠 (β ₁ ^+/+ ) 联合或不联合艾司洛尔(一种选择性 β ₁ -肾上腺素能受体阻滞剂) 或 β ₁ -肾上腺素能受体敲除小鼠 (β ₁ ^{– /–} )。手术后18小时，进行超声心动图检查，采集血液和脾脏，分析淋巴细胞功能。

测量和主要结果： 

在 18 小时，β ₁ ^+/+盲肠结扎和穿刺小鼠表现出高级别脓毒症的特征和三个免疫抑制的替代标志物，即脾脏 CD4 T 细胞减少、CD4 T 细胞增殖减少和调节性 T 淋巴细胞比例增加。药理学和遗传_β1-肾上腺素能受体阻断逆转了脓毒症对 CD4 T 和调节性 T 淋巴细胞比例的影响，并维持了 CD4 T 细胞增殖能力。β ₁-肾上腺素能受体阻断盲肠结扎和穿刺小鼠也表现出促炎和抗炎介质的整体减少，尽管预期心率会降低，但在维持心力指数的情况下提高了体内心血管效率。

结论： 

β ₁ -肾上腺素能受体激活增强了调节性 T 淋巴细胞抑制功能，因此有助于脓毒症诱导的免疫抑制。这可以通过 β _1-肾上腺素能受体阻断来减弱，这表明该疗法在脓毒症治疗中具有潜在的免疫调节作用。