title: Effect of interleukin-10 on the production of tumor necrosis factor-alpha by peripheral blood mononuclear cells from patients with chronic heart failure.
abstract: Chronic heart failure (HF) is a state of inflammatory immune activation characterized by elevated circulating levels of tumor necrosis factor-alpha (TNF-alpha). Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that inhibits TNF-alpha production and lessens endotoxin bioactivity. It is not known whether IL-10 reduces lipopolysaccharide (LPS) stimulated TNF-alpha production of peripheral blood mononuclear cells (PBMCs) from patients with chronic HF. PBMCs were isolated from 15 patients with chronic HF (New York Heart Association functional class 3.0 +/- 0.2, left ventricular ejection fraction 30 +/- 2%, peak oxygen consumption 18.1 +/- 0.8 ml/kg/min) and 15 healthy control subjects and stimulated with 1 and 10 ng/ml LPS for 24 hours with or without prior addition of IL-10 (10 ng/ml). TNF-alpha was quantified in cell-free supernatants by an enzyme-linked immunosorbent assay. TNF-alpha, soluble TNF receptors, IL-10, and LPS were quantified in plasma. LPS stimulated TNF-alpha production was highest in those patients in New York Heart Association class II (p <0.01 vs New York Heart Association class III and IV, p <0.001 vs control subjects). IL-10 reduced PBMC TNF-alpha production in all stimulated samples at 1 and 10 ng/ml LPS (mean reduction 43% at 1 ng/ml, p <0.01 and 55% at 10 ng/ml, p <0.0001). The percentage reduction in TNF-alpha release did not differ significantly between patients and control subjects or with respect to severity of chronic HF or baseline immune parameters. Independently of clinical severity, IL-10 profoundly inhibits TNF-alpha release from PBMCs isolated from patients with chronic HF. IL-10 is, therefore, a potential therapy for use in chronic HF associated with inflammatory immune activation.
authors.affiliation: Clinical Cardiology, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom. a.bolger@ic.ac.uk
authors.forename: Aidan P
authors.initials: AP
authors.lastname: Bolger
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sharma
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.forename: Brian
authors.initials: B
authors.lastname: Oliver
authors.forename: Mathias
authors.initials: M
authors.lastname: Rauchhaus
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Coats
authors.forename: Ian M
authors.initials: IM
authors.lastname: Adcock
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D002478:Cells, Cultured; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10