Neutrophils release more cytokines in DM, HFpEF patients

In patients with type 2 diabetes mellitus (DM) or heart failure with preserved ejection fraction (HFpEF), neutrophils seem to secrete more cytokines, contributing to low-grade chronic inflammation, a recent study reports.

The study includes 22 patients with DM, 15 with HFpEF, and 13 with both DM and HFpEF. Venous blood samples were collected from the participants and subjected to enzyme-linked immunosorbent assays to measure levels of cytokines; in vitro assays were used to determine the levels of cytokine release by isolated neutrophils. A parallel group of 21 healthy controls was also included.

Experiments revealed that circulating nitric oxide levels were significantly suppressed in DM (p≤0.001), HFpEF (p≤0.05), and HFpEF with DM (p≤0.001) patients, with an up to 44-percent difference relative to controls.

Meanwhile, circulating concentrations of the soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 rose up to 2.5-fold and 1.9-fold, respectively, in the HFpEF and HFpEF-DM subgroups (p≤0.001). E-selectin, in comparison, was increased only in patients with both conditions (p≤0.001).

Similarly, levels of other inflammatory markers, such as the C-reactive protein, interleukins (IL) 8 and 6, and interleukin-receptor antagonist, were significantly elevated in all three patient groups.

These findings were further bolstered by cell culture experiments, which showed that after lipopolysaccharide exposure, neutrophils from HFpEF with DM patients had increased secretion of IL-8 and IL-6 relative to controls, while cells from HFpEF patients showed impaired production of IL-1 receptor antagonist and vascular endothelial growth factor.

“A neutrophil-mediated pro-inflammatory response may play a pivotal role in the genesis and complications of HFpEF, and these findings deserve further investigation,” the researchers said.