0000000000210548
AUTHOR
Aidan P. Bolger
Whole blood endotoxin responsiveness in patients with chronic heart failure: the importance of serum lipoproteins.
Background Endotoxin [lipopolysaccharide (LPS)] may be an important stimulus for cytokine release in patients with chronic heart failure (CHF). We sought to investigate the relationship between whole blood endotoxin responsiveness and serum lipoprotein concentrations. It is not known if low-dose LPS is sufficient to stimulate immune activation. Methods and results Whole blood from 32 CHF patients (mean age 66±2 years, NYHA class 2.7±0.2, five female) and 11 healthy control subjects (mean age 47±4 years, six female) was stimulated with LPS at nine different concentrations (0.001 to 10 ng/mL), and tumor necrosis factor (TNF-α) release was quantified. Reference standard endotoxin at concentrat…
Pathophysiologic quantities of endotoxin-induced tumor necrosis factor-alpha release in whole blood from patients with chronic heart failure.
Bacterial endotoxin activity is elevated in patients with decompensated chronic heart failure (HF) and acts as a potent stimulus for immune activation. We sought to determine whether endotoxin, at an activity level seen in vivo (around 0.6 EU/ml), is sufficient to stimulate the secretion of tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha soluble receptor (sTNFR2) in ex vivo whole blood from patients with HF. We studied 15 patients with HF (aged 65 +/- 1.9 years, New York Heart Association class 2.1 +/- 0.3, left ventricular ejection fraction 31 +/- 5%; mean +/- SEM), of whom 5 had cardiac cachexia, and 7 healthy control subjects (59 +/- 5 years, p = NS). Reference endotoxin was added …
Effect of noradrenaline and isoproterenol on lipopolysaccharide-induced tumor necrosis factor-alpha production in whole blood from patients with chronic heart failure and the role of beta-adrenergic receptors
Increased levels of tumor necrosis factor-alpha (TNF-alpha) correlate with poor prognoses in chronic heart failure (CHF). This study demonstrated that noradrenaline and isoproterenol inhibit TNF-alpha production in patients with CHF in ex vivo whole blood in a dose-dependent fashion. The beta-blocker bisoprolol abolishes this effect.
Heat shock protein 70 in patients with chronic heart failure: relation to disease severity and survival
Heat shock protein 70 (Hsp70) is essential for cellular recovery, survival and maintenance of cellular function. Research into the possible use of Hsp70 as a cytoprotective therapeutic agent is ongoing. Chronic heart failure (CHF) is a state associated with systemic inflammation, particularly in patients with cardiac cachexia. We hypothesised that circulating Hsp70 levels are elevated in patients with CHF, more so in cachechtic patients, and that Hsp70 levels would relate to mortality.We studied 107 patients (28 female, age 67+/-1 years, NYHA class 2.6+/-0.6 and LVEF 29+/-1%, mean+/-SEM) and 21 controls. Cardiac cachexia was present in 32 patients. Hsp70 was detectable in 41% of CHF patient…
The relationship between age and production of tumour necrosis factor-α in healthy volunteers and patients with chronic heart failure
Ageing is associated with an altered immune response. Elevated plasma levels of tumour necrosis factor-alpha (TNF-alpha) are present in patients with advanced chronic heart failure (CHF). However, the relationship between age and the immune response in CHF is unknown.We investigated the relationship between age and the TNF-alpha generating capacity of lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) in nine healthy control subjects (mean age 51.6+/-3.6 years, age range 39-75 years) and 22 stable patients with CHF (mean age 68.3+/-1.5 years, age range 52-78 years, NYHA class 3.0+/-0.2). We also tested the TNF-alpha generating capacity of all control subjects and …
The anti-CD14 antibody IC14 suppresses ex vivo endotoxin stimulated tumor necrosis factor-alpha in patients with chronic heart failure
Background: Activation of the endotoxin (LPS) receptor, CD14, leads to tumor necrosis factor-alpha (TNF) production. Plasma LPS activity is elevated in patients with severe chronic heart failure (CHF). An anti-CD14 antibody, IC14, blocks TNF production in healthy volunteers. It is not known whether IC14 prevents TNF production in CHF patients. Methods and results: Blood from 20 CHF patients (age 64±2.1 years, NYHA class 2.2±0.1, LVEF 27±3%, mean±SEM) was pre-incubated with 0.5, 1.0, 5.0, 10 and 50 μg/mL IC14 for 1 h followed by incubation with 1 or 10 ng/mL LPS for 6 h. Fourteen subjects served as controls (58±2.4 years). LPS-stimulated TNF release was 76% and 60% greater at 1 and 10 ng/mL …