title: Activation of the NF-kappaB system in peripheral blood leukocytes from patients with chronic heart failure.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Cardiology Department, Military Hospital, ul. Weigla 5, 50-981 Wroclaw, Poland. Ewa.Jankowska@antro.pan.wroc.pl
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Jankowska
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Anna
authors.initials: A
authors.lastname: Czarny
authors.forename: Ewa
authors.initials: E
authors.lastname: Zaczynska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kus
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Waldemar
authors.initials: W
authors.lastname: Banasiak
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
mesh_terms: D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B