An increase of interleukin-33 serum levels after coronary stent implantation is associated with coronary in-stent restenosis

Abstract

The study aim was to determine the predictive value of interleukin (IL)-33, a recently described member of the IL-1 family of cytokines, for the development of in-stent restenosis (ISR). IL-33 serum levels were measured in 387 consecutive patients undergoing percutaneous coronary intervention (PCI) of whom 193 had stable angina, 93 non-ST elevation myocardial infarction (NSTEMI), and 101 ST-elevation MI (STEMI), respectively. Blood was taken directly before and 24h after stent implantation. The presence of ISR was initially evaluated by clinical means after six to eight months. When presence of myocardial ischemia was suspected, coronary angiography was performed to confirm the suspected diagnosis of ISR. Clinical ISR was present in total in 34 patients (8.8%). IL-33 was detectable in 185 patients and was below detection limit in 202 patients. In patients with decreased IL-33 (n=95), unchanged or non-detectable levels (n=210) or increased levels of IL-33 after PCI (n=82), ISR-rate was 2.1%, 9.5% and 14.6%, respectively (p<0.05). Accordingly, patients with ISR showed a significant increase of IL-33 upon PCI (p<0.05). This association was independent from clinical presentation and risk factors as well as numbers and type of stents. In patients with both stable and unstable coronary artery disease, an increase of IL-33 serum levels after stent implantation is associated with a higher rate of in-stent restenosis.

Keywords: Coronary artery disease; Interleukin-33; Myocardial infarction; Percutaneous coronary intervention; Restenosis.

Fig. 1

Restenosis rate according to the change of IL-33 serum levels. IL-33 serum levels were measured in the patients before and 24 h after PCI by ELISA as described under “Section 2”. In patients with decreased IL-33, unchanged or non-detectable (n.d.) levels or increased levels of IL-33 after PCI, in-stent restenosis (ISR) rate was 2.1%, 9.5% and 14.6%, respectively.

Fig. 2

Change in IL-33 levels according to the presence of ISR. IL-33 serum levels were measured in the patients before and 24 h after PCI by ELISA as described under “Section 2”. Changes in IL-33 serum levels are shown in accordance with presence (Yes) or absence (No) of in-stent restenosis (ISR) in the entire cohort (panel A) or patients with acute coronary syndrome (ACS; panel B) or stable coronary artery disease (CAD, panel C).