title: Elevated circulating levels of inflammatory cytokines and bacterial endotoxin in adults with congenital heart disease.
abstract: Chronic heart failure is a state of immune activation, and endotoxin is a potential trigger for cytokine production. Our aim was to study whether immune activation and endotoxemia occur in adults with congenital heart disease. We prospectively measured tumor necrosis factor (TNF)-alpha, soluble TNF receptors (sTNFR-1, sTNFR-2), interleukin-6, interleukin-10, endotoxin, and soluble CD14 levels in 52 consecutive adults with congenital heart disease (age 34 +/- 2 years [mean +/- SEM]) and 18 healthy controls (age 31 +/- 1 years). A variety of congenital heart lesions were studied: single ventricle physiology (n = 15), systemic right ventricle (n = 7), tetralogy of Fallot (n = 20), and "other" congenital heart disease (n = 10). Patients were subgrouped into asymptomatic (New York Heart Association [NYHA] class I, n = 11), mild (NYHA class II, n = 30), and moderate/severe (NYHA class III/IV, n = 11) categories. Patients had elevated TNF and interleukin-6 levels compared with controls (TNF 2.8 vs 2.1 pg/ml, p <0.05; interleukin-6 8.5 vs 5.7 pg/ml, p <0.001). TNF levels were higher in patients with moderate/severe symptoms compared with patients who were asymptomatic or had mild symptoms (p <0.05). Soluble TNFR-1 levels related directly to the degree of systemic ventricular impairment (p <0.05). There were no significant differences in sTNFR-1, sTNFR-2, interleukin-10, or sCD14 levels between patients and controls. Endotoxin levels were greater in patients with congenital heart disease versus controls (0.40 vs 0.26 endotoxin units/ml, p <0.0001). Thus, adults with congenital heart disease have elevated levels of inflammatory cytokines and bacterial endotoxin, which relate to functional status. Congenital heart disease in adults may be amenable to novel anti-inflammatory therapies in selected patients.
authors.affiliation: Department of Clinical Cardiology, National Heart & Lung Institute, Imperial College School of Medicine, London, UK. drsharmarakesh@aol.com
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sharma
authors.forename: Aidan P
authors.initials: AP
authors.lastname: Bolger
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Periklis A
authors.initials: PA
authors.lastname: Davlouros
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Philip A
authors.initials: PA
authors.lastname: Poole-Wilson
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Coats
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gatzoulis
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood; D000970:Antineoplastic Agents / Q000097:blood; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D019446:Endotoxemia / Q000097:blood* / Q000209:etiology / Q000276:immunology*; D004731:Endotoxins / Q000097:blood*; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood* / Q000150:complications / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10