Interleukin-1 receptor antagonist alters the response to vessel wall injury in a porcine coronary artery model.
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.
Morton
Allison C
AC
Cardiovascular Research Unit, Division of Clinical Sciences (Northern General Hospital), University of Sheffield, Sheffield S5 7AU, UK.
Arnold
Nadine D
ND
Gunn
Julian
J
Varcoe
Richard
R
Francis
Sheila E
SE
Dower
Steven K
SK
Crossman
David C
DC
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D023903:Coronary Restenosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D023921:Coronary Stenosis / Q000378:metabolism / Q000628:therapy; D003331:Coronary Vessels / Q000293:injuries* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D011897:Random Allocation; D012795:Sialoglycoproteins / Q000378:metabolism / Q000627:therapeutic use*; D013552:Swine; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins