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Background IL-37 emerges as a natural suppressor of inflammatory responses. The potential role of IL-37 in the pathology of atherosclerosis is unclear. The purpose of this study was to assess IL-37 profile in acute coronary syndrome (ACS) and the prognostic role of this cytokine in patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Methods In a case-control study, we prospectively enrolled 216 patients undergoing the first coronary angiography, which consisted of 5 groups: normal (n = 57), stable angina (SAP, n = 36), unstable angina (UAP, n = 42), non-STEMI (n = 36), STEMI (n = 45). Plasma IL-37, IL-6 and serum amyloid A (SAA) were measured using a commercially ELISA kit. Besides, in a prospective cohort study, 125 patients with STEMI of onset < 12 h undergoing PPCI were enrolled and divided into 2 groups according to the concentrations of IL-37 (< 341.1 pg/ml or ≥ 341.1 pg/ml). In-hospital major adverse cardiac event (MACE) including nonfatal myocardial infarction (MI), target lesion revascularization, acute heart failure, and cardiac death were estimated for prognosis. Results IL-37 was gradually increased in accordance with the severity of coronary artery disease. The circulating concentration of IL-37 was remarkably higher in the ACS patients than in either of the normal or SAP patients ( p < 0.05), and especially higher in the AMI patients including STEMI and non-STEMI than in the angina pectoris subjects no matter SAP or UAP ( p < 0.05). There was no statistical difference of IL-37 between normal and SAP patients, STEMI and non-STEMI patients ( p > 0.05). The trend of the change of IL-37 was consistent with that of SAA or IL-6. A higher circulating concentration of IL-37 before PPCI was accompanied with the decreased LVEF and the increased NT-proBNP concentrations, and independently predictive of in-hospital MACE rate in patients with STEMI undergoing PPCI (OR = 3.652, 95% CI = 1.113–11.983, p < 0.05). Conclusions We demonstrated the IL-37 profile in patients with acute coronary syndrome and the increased IL-37 concentration was associated with a worse clinical in-hospital outcome in STEMI patients undergoing PPCI. [ABSTRACT FROM AUTHOR]