© 2005 European Society of Cardiology
Activation of the NF-
B system in peripheral blood leukocytes from patients with chronic heart failure
a Cardiology Department, Military Hospital ul. Weigla 5, 50-981 Wroclaw, Poland
b Clinical Cardiology, National Heart and Lung Institute Imperial College, London, United Kingdom
c Institute of Immunology and Experimental Therapy, Polish Academy of Sciences Wroclaw, Poland
d Division of Applied Cachexia Research, Department of Cardiology Charite, Berlin, Germany
* Corresponding author. Tel./fax: +48 71 7660 250. E-mail address: Ewa.Jankowska{at}antro.pan.wroc.pl
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Abstract |
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Aim: To evaluate the activation of transcriptional nuclear factor kappa-B (NF-
B) in peripheral blood leukocytes (PBL) from patients with chronic heart failure (CHF). In vitro experiments were used to elucidate the role of lipopolysaccharide (LPS) as a stimulus for the NF-B system in PBL.
Methods and results: We examined 46 CHF patients (age: 62±1 years, LVEF: 31±1%, NYHA class: 2.7±0.1), 11 coronary artery disease (CAD) patients without CHF, and 13 healthy young subjects. The immunocytochemical localisation of NF-B in PBL was assessed using a polyclonal rabbit IgG anti-c-Rel-subunit antibody. NF-B activation was expressed as the percentage of PBL nuclei stained positively for c-Rel (NF-B(+)cell). PBL from healthy controls were exposed in vitro to the following concentrations of LPS from Escherichia coli (strain O111:B4): 0.1, 10 and 5000 ng/mL. CHF patients demonstrated the highest NF-B activation in PBL (NF-B(+)cells [%]: 37.1±1.5) as compared to CAD patients (29.1±3.0%) and controls (12.6±1.5%) (all p<0.05). There were three main clinical determinants of NF-B activation in PBL from CHF patients: peak oxygen consumption (r=0.53, p=0.025), presence of peripheral oedema (r=0.37, p<0.05) and serum C-reactive protein (r=0.40, p=0.02). In PBL from healthy subjects, LPS at all concentrations increased NF-B activity towards the pattern detected in CHF.
Conclusions: The NF-B system is highly overactive in PBL from CHF patients. LPS at low concentrations in peripheral blood may be involved in NF-B activation in PBL, and is a potential target for future therapeutic applications.
Key Words: Nuclear factor kappa-B • Immune activation • Chronic heart failure
Received October 25, 2004; Revised November 25, 2004; Accepted May 16, 2005
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