Beta blocker and angiotensin-converting enzyme inhibitor therapy is associated with decreased Th1/Th2 cytokine ratios and inflammatory cytokine production in patients with chronic heart failure
Beta blocker and angiotensin-converting enzyme inhibitor therapy is associated with decreased Th1/Th2 cytokine ratios and inflammatory cytokine production in patients with chronic heart failure
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DOI：
10.1159/000076766
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发表时间：
2004-01-01
影响因子：
2.4
通讯作者：
Vredevoe, DL
中科院分区：
文献类型：
--
作者：
Gage, JR;Fonarow, G;Vredevoe, DL
目的：研究β受体阻滞剂和血管紧张素转换酶（ACE）抑制剂（调节β肾上腺素能信号传导的药物）对慢性心力衰竭（HF）患者免疫功能的潜在影响。方法：对心力衰竭中心的 118 名患者进行了去甲肾上腺素 (NE)、T 细胞和炎症相关细胞因子白细胞介素 6 (IL-6) 循环水平的检测。在体外刺激 T 细胞后，在培养上清液中测量培养的外周血单核细胞 (PBMC) 产生的细胞因子干扰素-γ (IFNγ)、IL-10 和肿瘤坏死因子-α (TNFα) 的水平。结果：接受 ACE 抑制剂的患者的 NE 水平显着降低 (p = 0.0263)，接受 β 受体阻滞剂的患者的 NE 水平有降低的趋势。所有患者均表现出相对正常的 T 细胞水平，并且在接受任一类型药物治疗的患者中，总 (CD3+) 和辅助 (CD4+) T 细胞水平有较高水平（分别为 p = 0.0578 和 0.0932）。接受 β 受体阻滞剂和 ACE 抑制剂联合治疗的患者中 Th1 (IFNγ) 与 Th2 (IL-10) 细胞因子的比率较低 (p = 0.0373)。 NYHA 等级是血清 IL-6 的显着预测因子 (p < 0.0001)。接受两种药物治疗的患者血清 IL-6 水平有降低的趋势 (p = 0.0606)。在接受 ACE 抑制剂药物治疗的患者中，CD3/CD28 刺激的 PBMC 产生的 TNFα 显着降低 (p = 0.0223)。结论：这些结果表明，与慢性心力衰竭相关的高交感神经紧张会影响 Th1/Th2 和炎症细胞因子的产生，并且这些影响可以通过药物来调节。除了改善与心血管功能相关的临床参数外，β-受体阻滞剂和 ACE 抑制剂药物似乎也对心衰患者的免疫系统产生有益影响。版权所有 (C) 2004 S. Karger AG，巴塞尔。
Objective: To examine the potential impact of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, medications which modulate beta-adrenergic signaling, on immune function in patients with chronic heart failure (HF). Methods: 118 patients attending an HF center were tested for circulating levels of norepinephrine (NE), T cells and the inflammation-associated cytokine interleukin 6 (IL-6). Levels of the cytokines interferon-gamma (IFNgamma), IL-10, and tumor necrosis factor-alpha (TNFalpha) produced by cultured peripheral blood mononuclear cells (PBMC) were measured in culture supernatants following T cell stimulation in vitro. Results: NE levels were significantly lower in patients receiving ACE inhibitors (p = 0.0263), with a trend toward lower NE in patients receiving beta-blockers. All patients exhibited relatively normal levels of T cells, and there was a trend toward higher levels of total (CD3+) and helper (CD4+) T cells (p = 0.0578 and 0.0932, respectively) in patients receiving either type of medication. The ratios of Th1 (IFNgamma) to Th2 (IL-10) cytokines were lower in patients receiving a combination of beta-blocker and ACE inhibitor therapy (p = 0.0373). NYHA class was a significant predictor of serum IL-6 (p < 0.0001). There was a trend toward lower levels of serum IL-6 in patients receiving both types of medications (p = 0.0606). TNFalpha production by CD3/CD28-stimulated PBMC was significantly lower in patients receiving ACE inhibitor medications (p = 0.0223). Conclusions: These results suggest that high sympathetic tone associated with chronic HF affects Th1/Th2 and inflammatory cytokine production, and that these effects can be modulated by medications. In addition to improvement in clinical parameters relating to cardiovascular function, beta-blocker and ACE inhibitor medications also appear to have a beneficial effect on the immune system in HF. Copyright (C) 2004 S. Karger AG, Basel.