Interleukin-1beta modulation using a genetically engineered antibody prevents adverse cardiac remodelling following acute myocardial infarction in the mouse.

摘要

Adult male outbred ICR mice were purchased from Harlan Laboratories (Indianapolis, IN, USA). All animal experiments were conducted under the guidelines on Humane Use and Care of Laboratory Animals for bio-medical research published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996). The study protocol was approved by the Virginia Commonwealth University Institutional Animal Care and Use Committee. Thirty-six mice underwent experimental myocardial infarction as previously described.4 Briefly, mice were anaesthetized with intraperitoneal (IP) pentobarbital (70 mg/kg), intubated orotrache-ally, and ventilated on a positive-pressure ventilator. Left thoracotomy was performed at the fourth intercostal space and the heart was exposed by stripping the pericardium. The left descending coronary artery was then identified with a surgical microscope (Leica F40) and ligated with a 7.0 silk ligature. A group of four mice underwent sham operation as previously described. After surgery, mice were randomly assigned to treatment with XMA 052 MG1K, a genetically engineered antibody which consists of Human Engineered™ heavy and light chain variable regions fused to mouse Gamma-1 and Kappa constant regions that bind murine IL-13 with a high affinity, administered by IP injection at three different doses (0.05, 0.5, or 5 mg/kg) or a control murine lgG1 kappa antibody. .Treatments were administered immediately after surgery and then again 7 days later (n = 6 per group). One additional group of mice (n = 6) was used to test the effects of pre-treatment with an additional dose of XMA 052 MG1K (0.5 mg/kg), administered 48 h prior to surgery.