Krüger Stefan, Kunz Dagmar, Graf Jürgen, Stickel Tina, Merx Marc W, Koch Karl Christian, Janssens Uwe, Hanrath Peter
Medical Clinic I, University Hospital, University of Technology, Aachen, Germany.
Int J Cardiol. 2007 Feb 7;115(2):159-63. doi: 10.1016/j.ijcard.2006.03.003.
Raised concentrations of endotoxin (lipopolysaccharides, LPS) have been demonstrated in patients with chronic heart failure (CHF). Tolerance of monocytes to LPS can be induced by negative feedback mechanism through LPS itself, resulting in a downregulation of cytokine response to LPS challenge. As endotoxin desensitization has also been suggested for CHF, we investigated the response to LPS challenge in CHF patients.
We prospectively studied 100 patients with CHF (62 +/- 13 years) and 21 controls (58 +/- 10 years, LVEF 60 +/- 3%). HLA-DR expression and TNFalpha generation of monocytes after ex vivo stimulation by LPS (stimulation with LPS 50 and 500 pg/ml) were determined. 46 CHF patients were in NYHA class II (LVEF 29 +/- 8%) and 54 in NYHA class III (LVEF 27 +/- 7%).
HLA-DR expression in controls (25,837 +/- 7915 ABS/cell) was comparable to CHF NYHA II patients (23,720 +/- 8488 ABS/cell, n.s.), but lower in patients classified NYHA III (20,327 +/- 5073 ABS/cell, p < 0.01). Stimulated TNFalpha production ex vivo was higher in CHF NYHA III (LPS 50: 437 +/- 284; LPS 500: 946 +/- 500 pg/ml, each p < 0.05) and CHF NYHA II (LPS 50: 397 +/- 277; LPS 500: 933 +/- 483 pg/ml, each p < 0.05) compared to controls (LPS 50: 315 +/- 134; LPS 500: 715 +/- 339 pg/ml).
In chronic heart failure TNFalpha generation capacity increases while HLA-DR expression decreases compared to controls. Thus patients with CHF display enhanced susceptibility to inflammatory stimuli.
慢性心力衰竭（CHF）患者体内已证实内毒素（脂多糖，LPS）浓度升高。单核细胞对LPS的耐受性可通过LPS自身的负反馈机制诱导产生，导致细胞因子对LPS刺激的反应下调。由于也有人提出CHF存在内毒素脱敏现象，我们研究了CHF患者对LPS刺激的反应。
我们前瞻性地研究了100例CHF患者（62±13岁）和21名对照者（58±10岁，左心室射血分数[LVEF]60±3%）。测定了LPS体外刺激（用50和500 pg/ml LPS刺激）后单核细胞的HLA-DR表达和肿瘤坏死因子α（TNFα）生成情况。46例CHF患者为纽约心脏协会（NYHA）心功能II级（LVEF 29±8%），54例为NYHA心功能III级（LVEF 27±7%）。
对照者的HLA-DR表达（25,837±7915 ABS/细胞）与NYHA心功能II级的CHF患者（(23,720±8488 ABS/细胞，无统计学差异）相当，但在NYHA心功能III级患者中较低（20,327±5073 ABS/细胞，p<0.01）。与对照者（LPS 50：315±134；LPS 500：715±339 pg/ml）相比，NYHA心功能III级的CHF患者（LPS 50：437±284；LPS 500：946±500 pg/ml，各p<0.05）和NYHA心功能II级的CHF患者（LPS 50：397±277；LPS 500：933±483 pg/ml，各p<0.05）体外刺激后的TNFα生成量更高。
与对照者相比，慢性心力衰竭患者的TNFα生成能力增加而HLA-DR表达降低。因此，CHF患者对炎症刺激的易感性增强。
