Functional improvement in heart failure patients treated with beta-blockers is associated with a decline of cytokine levels

Mayer, Björn and Holmer, Stephan R. and Hengstenberg, Ch and Lieb, Wolfgang and Pfeifer, Michael and Schunkert, Heribert (2005) Functional improvement in heart failure patients treated with beta-blockers is associated with a decline of cytokine levels. INTERNATIONAL JOURNAL OF CARDIOLOGY, 103 (2). pp. 182-186. ISSN 0167-5273, 1874-1754

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Abstract

Background: In patients with severe heart failure (CHF), chronically elevated cytokine levels document a systemic inflammation. Experimental data suggest that activation of the beta-adrenergic system may participate in this inflammatory response. Herein, we studied as to whether beta-adrenergic blockade on top of standard CHIF therapy affects plasma cytokine levels (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF alpha]). Moreover, we studied if beta-blocker related changes of these cytokines correspond to changes in left ventricular (LV) function and exercise capacity. Methods: In a prospective study, 21 patients with stable CHIF (NYHA functional class II-III, ejection fraction < 40%, mean age 57.6 +/- 12.4 years) were treated with captopril (100-150 mg/day), furosemide (40-120 mg/day), and/or digoxin (0.1-0.2 mg/day) for at least I month before they entered a 4 week run-in period in which dosages were kept unchanged. Metoprololsuccinate was administered in increasing dosages (up to 190 mg/day) for the following 3 months. Clinical, echocardiographic, spiroergometric, and biochemical changes were assessed at the start and the end of the run-in period as well as after 3 month of beta-blockade. Results: As compared to 2 10 healthy volunteers, CHF patients, prior to beta-blockade, presented with markedly elevated IL-6 (8.9 +/- 9.9 vs. 2.1 +/- 0.5 pg/ml: p < 0.05) and TNF alpha levels (1.51 +/- 0.49 vs. 0.64 +/- 0.15 pg/ml; p < 0.05) levels. In CHF patients, 3 month of beta-blockade lowered heart rate (84 14 vs. 68 12 bpm; p < 0.01), systolic (131 +/- 7 vs. 118 +/- 6 mm Hg; p < 0.01), and diastolic blood pressure (78 +/- 5 vs. 71 +/- 6 mm Hg;p < 0.01). Spiroergometric determined VO2 max (17.8 +/- 4.5 vs. 19.8 +/- 4.3 ml/min kg;p=0.013) increased significantly during 3 month of beta-blockade. Moreover, LV functional parameters tended to improve but the interindividual response varied and changes were non-significant. Interestingly, IL-6 levels decreased markedly during beta-blockade (8.9 +/- 9.9 vs. 4.5 +/- 3.1 pg/ml; p=0.036), whereas TNF alpha levels remained unchanged. Moreover, significant positive correlations were found between decrease of IL-6 levels and left ventricular end diastolic diameters (r(2)=0.59; p=0.012), whereas an inverse correlation was found between the decrease of IL-6 and the increase of VO2 max (r(2)=0.54; p=0.037), respectively. Conclusion: In heart failure patients, beta-blockade may lower IL-6 but not TNFa levels. Changes of IL-6 during beta-blockade may be related to changes of LV function and geometry. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: TUMOR-NECROSIS-FACTOR; IDIOPATHIC DILATED CARDIOMYOPATHY; INTERLEUKIN-6 GENE-TRANSCRIPTION; RANDOMIZED INTERVENTION TRIAL; SERUM INTERLEUKIN-6; METOPROLOL CR; FACTOR-ALPHA; MERIT-HF; CARVEDILOL; RAT; IL-6; chronic heart failure; beta-blockers
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin II
Depositing User: Dr. Gernot Deinzer
Date Deposited: 03 May 2021 08:59
Last Modified: 03 May 2021 08:59
URI: https://pred.uni-regensburg.de/id/eprint/35768

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