Gage Julia R, Fonarow Gregg, Hamilton Michele, Widawski Mel, Martínez-Maza Otoniel, Vredevoe Donna L
Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, Calif., USA.
Neuroimmunomodulation. 2004;11(3):173-80. doi: 10.1159/000076766.
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).
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.
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).
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.
研究β受体阻滞剂和血管紧张素转换酶（ACE）抑制剂这两种调节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。
对118名就诊于心力衰竭中心的患者进行了去甲肾上腺素（NE）、T细胞以及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T细胞刺激后，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）在培养上清液中的水平。
接受ACE抑制剂治疗的患者NE水平显著降低（p = 0.0263），接受β受体阻滞剂治疗的患者NE水平有降低趋势。所有患者的T细胞水平相对正常，接受任一类型药物治疗的患者中，总T细胞（CD3+）和辅助性T细胞（CD4+）水平有升高趋势（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）。纽约心脏协会（NYHA）心功能分级是血清IL-6的显著预测指标（p < 0.0001）。接受两种药物治疗的患者血清IL-6水平有降低趋势（p = 0.0606）。接受ACE抑制剂治疗的患者中，CD3/CD28刺激的PBMC产生的TNFα显著降低（p = 0.0223）。
这些结果表明，与慢性HF相关的高交感神经张力会影响Th1/Th2和炎性细胞因子的产生，且这些影响可被药物调节。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抑制剂药物似乎对HF患者的免疫系统也有有益作用。
