Interleukin‐37 ameliorates myocardial ischaemia/reperfusion injury in mice

Summary Innate immune and inflammatory responses are involved in myocardial ischaemia/reperfusion ( I/R ) injury. Interleukin ( IL) ‐37 is a newly identified member of the IL ‐1 family, and functions as a fundamental inhibitor of innate immunity and inflammation. However, its role in myocardial I/R injury remains unknown. I/R or sham operations were performed on male C57BL/6J mice. I/R mice received an injection of recombinant human IL ‐37 or vehicle, immediately before reperfusion. Compared with vehicle treatment, mice treated with IL ‐37 showed an obvious amelioration of the I/R injury, as demonstrated by reduced infarct size, decreased cardiac troponin T level and improved cardiac function. This protective effect was associated with the ability of IL ‐37 to suppress production of proinflammatory cytokines, chemokines and neutrophil infiltration, which together contributed to a decrease in cardiomyocyte apoptosis and reactive oxygen species ( ROS ) generation. In addition, we found that IL ‐37 inhibited the up‐regulation of Toll‐like receptor ( TLR)‐ 4 expression and nuclear factor kappa B ( NF‐kB) activation after I/R , while increasing the anti‐inflammatory IL ‐10 level. Moreover, the administration of anti‐ IL ‐10 R antibody abolished the protective effects of IL ‐37 in I/R injury. In‐vitro experiments further demonstrated that IL ‐37 protected cardiomyocytes from apoptosis under I/R condition, and suppressed the migration ability of neutrophils towards the chemokine LIX . In conclusion, IL ‐37 plays a protective role against mouse myocardial I/R injury, offering a promising therapeutic medium for myocardial I/R injury.