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与轻度慢性心力衰竭相比,重度慢性心力衰竭患者细胞内单核细胞细胞因子的产生及CD14表达上调。

Intracellular monocyte cytokine production and CD 14 expression are up-regulated in severe vs mild chronic heart failure.

作者信息

Conraads Viviane M, Bosmans Johan M, Schuerwegh Annemie J, Goovaerts Inge, De Clerck Luc S, Stevens Wim J, Bridts Chris H, Vrints Christiaan J

机构信息

Department of Cardiology, University Hospital Antwerp (UIA), Antwerp, Belgium.

出版信息

J Heart Lung Transplant. 2005 Jul;24(7):854-9. doi: 10.1016/j.healun.2004.04.017.

Abstract

BACKGROUND

The role of circulating monocytes in the process of low-grade inflammation, characteristic of chronic heart failure (CHF), has recently been questioned. Lipopolysaccharide (LPS) desensitization has been proposed to mediate reduced monocyte cytokine elaboration in patients with severe CHF.

METHODS

Intracellular monocyte production of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha, and monocyte CD 14 expression were measured flow-cytometrically without and after 8-hour LPS stimulation in 46 patients with CHF and in a healthy control group.

RESULTS

Basal cytokine concentrations were similar for the control and the mild CHF groups (New York Heart Association [NYHA] Class I or II). After LPS stimulation, IL-6 (p=0.002) and TNF-alpha levels (p=0.001) were lower in the latter group, whereas IL-1 beta production was comparable. For the moderate-severe CHF patients, unstimulated IL-1 beta (p=0.04) was higher, whereas IL-6 (p=0.2) and TNF-alpha (p=0.1) levels were not different from the controls. Measurement of LPS-stimulated cytokine production showed no differences between the control group and patients with moderate-severe CHF (all p= 0.5). Upon comparing mild vs moderate-severe CHF patients, higher levels of unstimulated cytokine production (IL-1 beta, p=0.002; IL-6, p=0.01; TNF-alpha, p=0.003), stimulated IL-1 beta (p=0.002) and IL-6 (p=0.008) were found in the latter patients. CD 14 expression in the moderate-severe CHF group was higher than in the mild-CHF group (p = 0.03) and was strongly related to stimulated IL-1 beta (r=0.62, p<0.0001), IL-6 (r=0.56, p=0.0002) and TNF-alpha (r=0.41, p=0.006) production.

CONCLUSIONS

CD 14 expression and monocyte cytokine production, both unstimulated and after LPS stimulation, are increased in moderate-severe CHF when compared with mild CHF. These data suggest that circulating monocytes, possibly via increased CD 14 expression, may play a significant role in the immunologic dysbalance observed in advanced CHF.

摘要

背景

循环单核细胞在慢性心力衰竭(CHF)所特有的低度炎症过程中的作用最近受到质疑。有人提出脂多糖(LPS)脱敏可介导重度CHF患者单核细胞细胞因子分泌减少。

方法

采用流式细胞术测定46例CHF患者和一个健康对照组在未进行LPS刺激时以及8小时LPS刺激后细胞内单核细胞白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子(TNF)-α的产生情况以及单核细胞CD14的表达。

结果

对照组和轻度CHF组(纽约心脏协会[NYHA]I级或II级)的基础细胞因子浓度相似。LPS刺激后,后一组的IL-6(p=0.002)和TNF-α水平(p=0.001)较低,而IL-1β的产生相当。对于中度至重度CHF患者,未刺激的IL-1β(p=0.04)较高,而IL-6(p=0.2)和TNF-α(p=0.1)水平与对照组无差异。LPS刺激后细胞因子产生的测量结果显示对照组与中度至重度CHF患者之间无差异(所有p=0.5)。比较轻度与中度至重度CHF患者时,发现后一组未刺激的细胞因子产生水平(IL-1β,p=0.002;IL-6,p=0.01;TNF-α,p=0.003)、刺激后的IL-1β(p=0.002)和IL-6(p=0.008)更高。中度至重度CHF组的CD14表达高于轻度CHF组(p = 0.03),且与刺激后的IL-1β(r=0.62,p<0.0001)、IL-6(r=0.56,p=0.0002)和TNF-α(r=0.41,p=0.006)产生密切相关。

结论

与轻度CHF相比,中度至重度CHF患者未刺激时以及LPS刺激后的CD14表达和单核细胞细胞因子产生均增加。这些数据表明,循环单核细胞可能通过增加CD14表达,在晚期CHF中观察到的免疫失衡中发挥重要作用。

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