The enhanced plasma levels of soluble tumor necrosis factor receptors (sTNF‐R1; sTNF‐R2) and interleukin‐10 (IL‐10) in patients suffering from chronic heart failure are reversed in patients treated with β‐adrenoceptor antagonist

Abstract

1 Cytokines may parallel or regulate the beneficial effects of beta-adrenoceptor antagonist treatment observed in chronic heart failure (CHF) patients. Therefore, this study was performed in order to investigate alterations of cytokine levels in beta-blocker-treated patients suffering from CHF. 2 We investigated plasma cytokine levels in eight healthy controls and 12 CHF patients. The patients were treated with standard medication (CHFstd) or with standard medication and additional beta1-blocker metoprolol (CHFmet). Interleukin-(IL)-1alpha, IL-1beta, IL-1 receptor antagonist (IL-1ra), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF), soluble TNF receptor type 1 (sTNF-R1), sTNF-R2, and sCD14 were measured by ELISA. 3 IL-1alpha and IL-1beta were not detectable in any of the tested groups. IL-2, TNF, or sCD14 were not altered as compared with healthy control subjects. CHFstd patients expressed enhanced IL-1ra, IL-6, IL-8, IL-10, sTNF-R1 and sTNF-R2. In CHFmet patients IL-1ra, IL-6 and IL-8 remained at the same level. In contrast, sTNF-R1 levels were significantly reduced, although not to control, whereas the sTNF-R2 and IL-10 were reduced to control levels. 4 The cAMP levels of mononuclear cells--recalculated for the patients included in this study from previous work [Werner et al. (2001). Basic Res. Cardiol., 96, 290]--correlated inversely with the sTNF-R2 data (Pearson, r = -0.46; P = 0.041; Spearman, r = -0.64, P = 0.002). 5 The present data indicate an interaction of the neurohumoral and the cytokine system in CHF patients at the cAMP level. Thus, measurement and correlation of sTNF-R2 and cAMP may provide a tool useful during investigation of beta-blocker therapy.

Beta-Blockade Does Not Alter Plasma Cytokine Concentrations and Ventricular Function in Young Adults With Right Ventricular Dysfunction Secondary to Operated Congenital Heart Disease

“…Endothelin-1 concentrations were also higher than the normal range levels, but were not changed throughout the study in both the placebo and bisoprolol group. Since we have found previously that sTNF receptors were enhanced in CHF patients and reduced after -blocker treatment, 15,19 we also measured the effect of -blocker therapy on soluble TNF receptor and IL-6 concentrations in the patients included in the present study. The plasma concentrations of IL-6, sTNF-R1 and sTNF-R2 were not enhanced in the tested patients, as compared with normal range and remained at normal concentrations after treatment.…”

“…15 In the previous study, we documented that patients treated with metoprolol had a markedly improved left ventricular ejection fraction and significantly reduced cytokine concentrations. In contrast to these findings, in our present study the ejection fraction of the left ventricle remained unchanged.…”

“…5,16,31,32 It has been proposed that cytokines, such as soluble TNF receptors, parallel or mediate the beneficial effects ofadrenoceptor antagonist treatment observed in chronic heart failure patients with LVD. 14,15 No data exist about the cytokine concentrations and -blocker effect on ventricular function in ACHD with right ventricular volume and/or pressure overload. Thus, we performed a prospective, randomized, double-blind, placebo-controlled study forblocker therapy of heart failure in patients with operated TOF.…”

“…15,21,23 Some publications showed that -blocker therapy improved ventricular func- tion and that the plasma concentrations of the treated patients contained reduced cytokine concentrations. 5,16,31,32 It has been proposed that cytokines, such as soluble TNF receptors, parallel or mediate the beneficial effects ofadrenoceptor antagonist treatment observed in chronic heart failure patients with LVD.…”

“…[8][9][10][11] Previous results obtained by us and other researchers showed that soluble tumor necrosis factor receptors (sTNF-R) and other cytokines are reduced in adult CHF patients treated with -blockers. [12][13][14][15][16][17][18] From these data it was concluded that cytokines might be involved in, or accompany, the beneficial effects of -blocker therapy. In pre-operated infants with heart failure resulting from left-toright shunts, we showed enhanced sTNF-R concentrations, which were reduced after propranolol treatment.…”