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

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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)-α, 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.

Section snippets

Patient population

We performed a prospective cross-sectional study assessing immunologic parameters in 52 consecutive adults with congenital heart disease (age 34 ± 2 years, 28 women; New York Heart Association [NYHA] class 2.0 ± 0.1) and 18 healthy age-matched control subjects (age 31 ± 1 years, 9 women; Table 1). Control subjects were recruited from staff members and their relatives at the Royal Brompton Hospital, none of whom were taking any medication or had any preexisting medical disorder. Patients with a

Results

Clinical details of the patients and controls are listed in Table 1; results from the cytokine parameters and endotoxin levels are listed in Table 2. There was no significant difference in mean age or the ratio of men to women between patient and control groups (all p >0.3). Patients were noted to have a significantly lower weight (p <0.05), with a trend toward a lower percent ideal body weight (p = 0.07) compared with controls. Patients with moderate to severe symptoms had significantly lower

Discussion

This study shows that there is immune activation in adult patients with congenital heart disease compared with healthy controls. Furthermore, patients with the most advanced disease have the greatest degree of inflammatory cytokine activation and endotoxemia (FIGURE 1, FIGURE 2). Patients with edema, in particular, were noted to have a significant increase in endotoxin activity compared with the patients without edema (Figure 2). Although sTNFR concentrations were not significantly increased in

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Dr. Sharma was supported by the Robert Luff Foundation, London, United Kingdom. Dr. Bolger and the Department of Cardiac Medicine were supported by the British Heart Foundation, London, United Kingdom. Dr. Coats was supported by the Viscount Royston Trust Fund, London, United Kingdom.

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