Inhibition of IL18 inhibits intimal hyperplasia after balloon injury - in an atherosclerotic rabbit model -

Objectives: Interleukin 18 (IL18) is an interferon (IFN)-gamma-inducing factor and a proinflammatory and pro-atherogenic cytokine. IL18 binding protein (IL18BP) functions as an IL18 inhibitor. This study was designed to investigate whether administration IL18BP could inhibit neointimal hyperplasia (NH) and artery lipid deposition.
Methods: Rabbit (fifty NZW, Male) were fed with 21% fat, 0.15% cholesterol. The left superficial femoral artery was de-endotheliazed with 2F arterial embolectomy catheter. IL18BP (5ug, 10ug or 25ug), or 0.9% saline (control) was administered IV bolus during surgery. Rabbits were followed-up at 2 and 4 weeks. Intima-media (I/M) and lumen-whole artery (L/W) ratios were calculated. Blood lipid panel and liver and kidney functions were evaluated. The extent of lipid deposition to artery was evaluated with ORO staining. Statistics was performed by ANOVA for mixed models using SAS and SPSS.
Results: Intravenous IL18BP 5ug, 10ug and 25ug significantly inhibited I/M ratios compared to control group at both 2wk and 4wk. There was no statistical difference between 5ug and 10ug groups. IL18BP 10ug significantly improved lumen area (L/A ratio) as compared to control and 5ug groups. Lipid panels were significantly elevated at 4wk and 6wk after fatty diet. IL18BP decreased the lipid deposition to artery.
Conclusion: IL18 BP inhibited NH and preserved the lumen area post arterial injury, as well as decreased lipid deposition to artery. This study could lead to future clinical application.