Interleukin-6 signaling in patients with chronic heart failure treated with cardiac resynchronization therapy

Abstract

IntroductionIncreased 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 methodsThe 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.ResultsThe 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).ConclusionsHF-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.

Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure

“…Recent evidence has revealed that inflammation is a critical pathological process of CHF (Dick and Epelman, 2016; Ayoub et al, 2017; Cocco et al, 2017) and high levels of IL-6, a proinflammatory cytokine, have been reported to be an important mediator in chronic inflammatory and cardiovascular disorders (Smart et al, 2006; Bacchiega et al, 2017). Moreover, IL-6 exerts its action through a specific IL-6R and a soluble IL-6 receptor, whereby the IL-6/IL-6R complex binds to the membrane glycoprotein 130 to induce intracellular signaling pathways (Hirota et al, 2004; Ptaszynska-Kopczynska et al, 2017). The JAK-STAT pathway is a characteristic signal transduction pathway that plays a crucial role in this process (Mohri et al, 2012).…”

Clinical manifestations of device-related infective endocarditis in cardiac resynchronization therapy recipients

“…Modified Duke lead criteria p = 0.003 relatively low specificity, and thus some new, cardiac specific markers might be more useful [16,17]. Nevertheless, our observations indicate that CDRIE should be suspected in every CRT patient who did not respond well to antibiotic therapy, has recurrent fever or has increased markers of infection.…”

Immune Response in Decompensated Chronic Heart Failure of Ischemic Origin

“…Повышенная экспрессия IL-6 в миокарде наблюдается на конечной стадии ХСН как ишемической, так и не ишемической этиологии. Интересно и то, что сигнальная передача gp130, связанная с IL-6, может быть кардиозащитной, тогда как чрезмерная активация gp130 приводит к прогрессированию ХСН [27].…”