Interleukin-6 signaling in patients with chronic heart failure treated with cardiac resynchronization therapy
Katarzyna Ptaszynska-Kopczynska1, Anna Szpakowicz1, Marta Marcinkiewicz-Siemion1
1Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
Insights
Patients with heart failure with reduced ejection fraction (HF-REF) exhibit elevated interleukin-6 (IL-6) and reduced soluble IL-6 receptor (sIL-6R). Cardiac resynchronization therapy (CRT) improves HF-REF, associated with smaller sIL-6R changes.
Area of Science:
- Cardiology
- Immunology
- Biochemistry
Background:
- Interleukin-6 (IL-6) is implicated in left ventricular dysfunction in chronic heart failure (CHF).
- Cardiac resynchronization therapy (CRT) can reverse CHF progression in patients with reduced ejection fraction (HF-REF).
Purpose of the Study:
- To investigate the IL-6 system, including soluble IL-6 receptor (sIL-6R) and soluble glycoprotein 130 (sgp130), in HF-REF patients.
- To evaluate the impact of CRT on these markers and their correlation with clinical status.
Main Methods:
- Serum IL-6, sIL-6R, and sgp130 levels were measured using ELISA in 88 HF-REF patients and 35 controls.
- Forty-five HF-REF patients received CRT and were followed for 6 months.
Main Results:
- HF-REF patients showed higher IL-6 and lower sIL-6R compared to controls (p=0.03 and p=0.008, respectively).
- IL-6 levels correlated negatively with ejection fraction (EF) and positively with BNP and CRP.
- Positive CRT responders had smaller changes in sIL-6R concentration post-therapy (p=0.04).
Conclusions:
- HF-REF is characterized by an altered IL-6 system with increased IL-6 and decreased sIL-6R.
- IL-6 levels reflect the clinical status of HF-REF patients.
- CRT-induced functional improvement in HF-REF is linked to attenuated sIL-6R changes.
Introduction:
Increased expression of interleukin-6 (IL-6) has been described in left ventricular dysfunction in the course of chronic heart failure. Cardiac resynchronization therapy (CRT) is a unique treatment method that may reverse the course of chronic heart failure (CHF) with reduced ejection fraction (HF-REF). We aimed to evaluate the IL-6 system, including soluble IL-6 receptor (sIL-6R) and soluble glycoprotein 130 (sgp130), in HF-REF patients, with particular emphasis on CRT effects.
Material And Methods:
The study enrolled 88 stable HF-REF patients (63.6 ±11.1 years, 12 females, EF < 35%) and 35 comorbidity-matched controls (63.5 ±9.8 years, 7 females). Forty-five HF-REF patients underwent CRT device implantation and were followed up after 6 months. Serum concentrations of IL-6, sIL-6R and sgp130 were determined using ELISA kits.
Results:
The HF-REF patients had higher IL-6 (median: 2.6, IQR: 1.6-3.8 vs. 2.1, IQR: 1.4-3.1 pg/ml, p = 0.03) and lower sIL-6R concentrations compared to controls (median: 51, IQR: 36-64 vs. 53. IQR 44-76 ng/ml, p = 0.008). There was no significant difference between sgp130 concentrations. In the HF-REF group IL-6 correlated negatively with EF (r = -0.5, p = 0.001) and positively with BNP (r = 0.5, p = 0.008) and CRP concentrations (r = 0.4, p = 0.02). Patients who presented a positive response after CRT showed a smaller change of sIL-6R concentration compared to nonresponders (ΔsIL-6R: -0.2 ±7.1 vs. 7 ±14 ng/ml; p = 0.04).
Conclusions:
HF-REF patients present higher IL-6 and lower sIL-6R levels. IL-6 concentration reflects their clinical status. CRT-related improvement of patients' functional status is associated with a smaller change of sIL-6R concentration in time.
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