Interleukin‑37 is increased in peripheral blood mononuclear cells of coronary heart disease patients and inhibits the inflammatory reaction

Abstract

It has been universally acknowledged that interleukin-37 (IL-37) has an immunosuppressive effect on various inflammatory disorders. However, whether IL‑37 participates in the acute inflammation associated with coronary heart disease (CHD) has not yet been clarified. In the present study, the association between the serum levels of IL-37 and the clinical indexes of CHD were analysed. In addition, the anti‑inflammatory effects of IL‑37 on peripheral blood mononuclear cells (PBMCs) were studied in CHD patients. PBMCs from 46 healthy controls (HCs) and 92 CHD patients were cultured in vitro and stimulated using the recombinant IL-37 protein. The protein levels, as well as the mRNA expression of inflammatory cytokines (TNF‑α, IL-1β, IL-6, and IL-17) were analysed by enzyme-linked immunosorbent assay (ELISA) and real‑time polymerase chain reaction (RT‑PCR). Spearman's correlation test was performed to examine the association between the serum level of IL-37 and the levels of pro-inflammatory cytokines, certain clinical indexes, and disease activity during CHD. Compared to the HCs, the CHD patients, especially those with acute myocardial infarction, exhibited higher levels of IL-37 in their PBMCs and sera. Serum levels of IL‑37 were associated with the levels of IL‑17, IL‑6, and TNF‑α, and clinical indexes such as the left ventricular ejection fraction (LVEF), amino‑N‑terminal pro-plasma brain natriuretic peptide (NT-proBNP) levels, and cardiac troponin T (cTnT) levels in CHD patients. Compared to the HC group, the production of inflammatory cytokines such as IL‑17, IL‑6, TNF‑α, and IL-1β increased in the PBMCs of CHD patients and significantly decreased after the stimulation of the cells with recombinant IL‑37. The IL‑37 levels in CHD patients were high, and were correlated with the levels of CHD‑related pro‑inflammatory cytokines and disease activity. Notably, the expression of CHD‑related pro‑inflammatory cytokines in the PBMCs of CHD patients decreased following the stimulation of the cells with recombinant IL‑37, indicating that IL‑37 exerts anti‑inflammatory effects during CHD.