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.