Aim: To evaluate the activation of transcriptional nuclear factor kappa-B (NF-kappaB) 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-kappaB 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-kappaB in PBL was assessed using a polyclonal rabbit IgG anti-c-Rel-subunit antibody. NF-kappaB activation was expressed as the percentage of PBL nuclei stained positively for c-Rel (NF-kappaB+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-kappaB activation in PBL (NF-kappaB+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-kappaB 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-kappaB activity towards the pattern detected in CHF.
Conclusions: The NF-kappaB system is highly overactive in PBL from CHF patients. LPS at low concentrations in peripheral blood may be involved in NF-kappaB activation in PBL, and is a potential target for future therapeutic applications.