Morton Allison C, Arnold Nadine D, Gunn Julian, Varcoe Richard, Francis Sheila E, Dower Steven K, Crossman David C
Cardiovascular Research Unit, Division of Clinical Sciences (Northern General Hospital), University of Sheffield, Sheffield S5 7AU, UK.
Cardiovasc Res. 2005 Dec 1;68(3):493-501. doi: 10.1016/j.cardiores.2005.06.026. Epub 2005 Aug 15.
To determine the influence of IL-1 on the arterial response to experimental injury in porcine models of percutaneous coronary intervention (PCI).
An intravenous (i.v.) bolus of 0.5 mg/kg followed by a subcutaneous (s.c.) infusion of 2 mg/kg/24 h of human IL-1 receptor antagonist (IL-1ra) inhibited neutrophil recruitment in response to intradermal IL-1. Using this dose regimen, five groups of pigs were studied: Group 1, oversized balloon angioplasty of 2 coronary vessels (14-day infusion, 28th day sacrifice and analysis); Groups 2, 3, 4, and 5, oversized stenting of 2 coronary vessels (Group 2: 14-day infusion, 28th day analysis; Group 3: 14-day infusion, 14th day analysis; Group 4: 28-day infusion, 28th day analysis; Group 5: 28-day infusion, 90th day analysis). Neointimal area was quantified by standard means.
In Group 1, IL-1ra resulted in a 23% decrease in neointimal area (p=0.04); in Group 2, a 34% increase (p=0.001); in Group 3, a 38% decrease (p<0.0001); in Group 4, a 34% decrease (p=0.0004); and in Group 5, a 41% decrease (p=0.00001).
IL-1ra was associated with a sustained, significant reduction in neointima after vessel wall injury as long as it is given for the duration of the stimulation of the IL-1 system, in this case at least 28 days. This suggests that therapies based on the antagonism of IL-1 may modulate the coronary artery response to injury.
确定白细胞介素-1（IL-1）对猪经皮冠状动脉介入治疗（PCI）实验模型中动脉损伤反应的影响。
静脉推注0.5mg/kg人白细胞介素-1受体拮抗剂（IL-1ra），随后皮下输注2mg/kg/24h，可抑制对皮内注射IL-1的中性粒细胞募集。采用该剂量方案，对五组猪进行研究：第1组，对2支冠状动脉进行超大球囊血管成形术（14天输注，第28天处死并分析）；第2、3、4和5组，对2支冠状动脉进行超大支架置入术（第2组：14天输注，第28天分析；第3组：14天输注，第14天分析；第4组：28天输注，第28天分析；第5组：28天输注，第90天分析）。通过标准方法对新生内膜面积进行定量分析。
在第1组中，IL-1ra使新生内膜面积减少23%（p=0.04）；在第2组中，增加34%（p=0.001）；在第3组中，减少38%（p<0.0001）；在第4组中，减少34%（p=0.0004）；在第5组中，减少41%（p=0.00001）。
只要在IL-1系统受刺激期间给予IL-1ra（在本研究中至少28天），其与血管壁损伤后新生内膜的持续、显著减少相关。这表明基于IL-1拮抗作用的治疗可能调节冠状动脉对损伤的反应。
