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Cardiovascular Research 2005 68(3):493-501; doi:10.1016/j.cardiores.2005.06.026
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Copyright © 2005, European Society of Cardiology

Interleukin-1 receptor antagonist alters the response to vessel wall injury in a porcine coronary artery model

Allison C. Mortona, Nadine D. Arnolda, Julian Gunna, Richard Varcoeb, Sheila E. Francisa, Steven K. Dowerc and David C. Crossmana,*

aCardiovascular Research Unit, Division of Clinical Sciences (Northern General Hospital), University of Sheffield, Sheffield, S5 7AU, UK
bDepartment of Molecular Physiology, University of Sheffield, Sheffield, UK
cDivision of Genomic Medicine, University of Sheffield, Sheffield, UK

* Corresponding author. Tel.: +44 114 271 5814; fax: +44 114 261 9587. Email address: d.c.crossman{at}sheffield.ac.uk

Objective: To determine the influence of IL-1 on the arterial response to experimental injury in porcine models of percutaneous coronary intervention (PCI).

Methods: 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.

Results: 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).

Conclusions: 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.

KEYWORDS Angioplasty/coronary intervention; Inflammation; Interleukins; Restenosis

Time for primary review 18 days


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