Neutrophils pro‐inflammatory and anti‐inflammatory cytokine release in patients with heart failure and reduced ejection fraction

Abstract

Aims Heart failure with reduced ejection fraction (HFrEF) is characterized by sub-clinical inflammation. Changes in selected biomarkers of inflammation concomitant with the release of pro-inflammatory and anti-inflammatory cytokines by neutrophils have not been investigated in patients with HFrEF. Methods and results Fifty-two patients, aged 68.8 ± 1.7 years, with HFrEF and left ventricular ejection fraction 28.7 ± 1.0%, and 21 healthy controls (CTL) were recruited. Twenty-five HF patients had type 2 diabetes. Venous blood samples from HF and CTL were collected once. Neutrophil-derived pro-inflammatory and anti-inflammatory cytokine levels were assessed in plasma by ELISA. Plasma biomarkers assessed included: C-reactive protein (CRP), vascular endothelial growth factor (VEGF), interleukins (IL)-6, -8, -1 receptor antagonist (-1RA), nitric oxide (NO), soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and E-Selectin (sE-Sel). Neutrophils were isolated and stimulated with various agonists to promote VEGF, IL-6, IL-8, and IL-1RA release. Compared with CTL, HFrEF patients showed a marked decrease in circulating VEGF [178.0 (interquartile range; IQR 99.6; 239.2) vs. 16.2 (IQR 9.3; 20.2) pg/mL, P ≤ 0.001] and NO [45.2 (IQR 42.1; 57.6) vs. 40.6 (IQR 30.4; 47.1) pg/mL, P = 0.0234]. All other circulating biomarkers were significantly elevated. Neutrophils isolated from patients with HFrEF exhibited a greater IL-8 release in response to LPS [1.2 ± 0.1 (CTL); 10.4 ± 1.6 ng/mL (HFrEF) and 12.4 ± 1.6 ng/mL (HFrEF and DM), P ≤ 0.001]. IL-6 release in response to LPS was not changed in HFrEF patients without diabetes, whereas it was significantly increased in patients with HFrEF and diabetes [46.7 ± 3.9 (CTL) vs. 165.8 ± 48.0 pg/mL (HFrEF),

Neutrophils and Circulating Inflammatory Biomarkers in Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction

“…23 We also reported that in the presence of HF and DM, both IL-6 and IL-8 concentrations were significantly increased. These observations agree with our previous work 9 and other independent studies, reporting that IL-6 and IL-8 play a significant role in HF and DM. 2,24 We reported a significant increase in the circulating antiinflammatory and antiproliferative cytokine IL-1RA, a member of the IL-1 family, 25 in patients with DM and/or HF (DM, HFpEF, and HFpEF + DM).…”

“…Neutrophils were isolated by dextran sedimentation followed by Ficoll-Paque density gradient as described previously. 9 Peripheral blood mononuclear cells were <0.1% as determined by morphological analysis and flow cytometry (data not shown), and viability was >98% (trypan blue dye exclusion). 9 Pure neutrophil population (>99%) was used for in vitro studies.…”

“…9 Peripheral blood mononuclear cells were <0.1% as determined by morphological analysis and flow cytometry (data not shown), and viability was >98% (trypan blue dye exclusion). 9 Pure neutrophil population (>99%) was used for in vitro studies.…”

“…Donors were informed about the procedures and signed a written informed consent before participating in the study. Because all data (blood samples and demographics) from the CTL volunteers have also been reported in our recently published manuscript, 9 we acknowledge that in the current manuscript, we reported the same data for CTL (John Wiley and Sons publisher license #5254220160933).…”

Serum Cytokines as Biomarkers in Heart Failure with Preserved Ejection Fraction and Sleep Apnea: A Prospective Cohort Study

“…In a large cohort of HF patients, elevated IL-6 levels were detected in more than 50% of patients [ 37 ]. In a recent study, patients with HFrEF exhibited a significant decrease in circulating VEGF [ 38 ]. IL-10 levels were also shown to be increased in HF patients [ 39 ].…”