Interleukin 6 Signalling in Heart Failure With Preserved and Reduced Ejection Fraction

Identification of interleukin-6 (IL-6) signaling pathways in patients with chronic heart failure (CHF).

The diversity of IL-6 effects is due to the presence of classical signaling and trans-signaling pathways. The study included 164 patients with CHF hospitalized for acute decompensated heart failure (ADHF), of which 129 had reduced left ventricular ejection fraction (HFrEF), and 35 had preserved ejection fraction (HFpEF). Blood concentrations of IL-6, soluble IL-6 receptor (sIL-6R), soluble transducer protein gp130 (sgp130), and high-sensitivity C-reactive protein (hsCRP) were measured.

Patients with HFpEF had lower concentrations of IL-6 (6.15 [2.78, 10.65] pg/ml) and hsCRP (11.27 [5.84, 24.40] mg/ml) than patients with HFrEF (9.20 [4.70; 15.62] pg/ml and 17.23 [8.70; 34.51 mg/ml], respectively). In contrast, concentrations of rIL-6R were higher in HFpEF (59.06 [40.00; 75.85] ng/ml) than in HFrEF (49.15 [38.20; 64.89] ng/ml). Concentrations of sgp130 were not significantly different. In patients with HFrEF, positive correlations were found between the concentrations of IL-6 and hsCRP, IL-6 and rIL-6R, and IL-6 and sgp130, while in patients with HFpEF, there was a correlation only between IL-6 and hsCRP, which appeared stronger than in patients with HFrEF (r=0.698; p<0.001 and r=0.297; p<0.05, respectively).

Classical IL-6 signaling and trans-signaling are expressed to different degrees in patients with HFrEF and HFpEF in ADHF. The results of the study supplement the existing knowledge about the pathogenesis of inflammation in CHF and may contribute to the development of new methods and approaches to the treatment of the disease.