Elevated plasma interleukin-37 playing an important role in acute coronary syndrome through suppression of ROCK activation

OBJECTIVE: The plasma level of interleukin-37 is elevated in patients with acute coronary syndrome, however, its function during the onset and progress of the disease remains unclear. This study aimed to investigate the clinical significance of IL-37 in acute coronary syndrome and its underlying mechanism. METHODS: 124 patients with acute coronary syndrome and 40 healthy controls were recruited in this study. Plasma interleukin-37 levels were measured in 41 patients with ST elevation myocardial infarction (STEMI), 41 patients with non-STEMI, 42 patients with unstable angina, and 40 controls. Mortality was defined as an event. RESULTS: In this study, the mean follow-up period was 824±306 days (2-1077 days). 22% (n=27) of patients died. The mortality rate was significantly lower in patients with interleukin-37 serum levels below the median (6.4 pg/mL) than those with interleukin-37 serum levels above 6.4 pg/mL at 36-month follow-up (16% vs. 24%, p=0.02, log rank X(2)=5.39). Highly concentration of the anti-inflammatory interleukin-37 exerted a protective effect by suppressing the activated Rho Kinase (ROCK) activity in the peripheral blood mononuclear cells in vivo and in vitro after ischemia/reperfusion injury and stimulation of the Rho activator, calpeptin. CONCLUSIONS: The interleukin-37 level is significantly increased in acute coronary syndrome. Elevated baseline interleukin-37 levels in patients on admission are associated with poor outcomes. Thus, we propose that interleukin-37 could be a biomarker predictive of mortality in acute coronary syndrome. Moreover, this study reveals that the protective effect of interleukin-37 against atherosclerosis may involve the inhibition of ROCK activity.