Elevated circulating levels of inflammatory cytokines and bacterial endotoxin in adults with congenital heart disease

Am J Cardiol. 2003 Jul 15;92(2):188-93. doi: 10.1016/s0002-9149(03)00536-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / blood
  • Antineoplastic Agents / blood
  • Cross-Sectional Studies
  • Cytokines / blood*
  • Endotoxemia / blood*
  • Endotoxemia / etiology
  • Endotoxemia / immunology*
  • Endotoxins / blood*
  • Female
  • Heart Defects, Congenital / blood*
  • Heart Defects, Congenital / complications
  • Heart Defects, Congenital / immunology*
  • Humans
  • Inflammation / blood*
  • Inflammation / complications
  • Inflammation / immunology*
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Lipopolysaccharide Receptors / blood
  • Male
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor / blood
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / analysis


  • Antigens, CD
  • Antineoplastic Agents
  • Cytokines
  • Endotoxins
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • Interleukin-10