Temporal and spatial distribution of interleukin-1 beta in balloon injured porcine coronary arteries.
OBJECTIVE
Interleukin-1 beta (IL-1 beta) is a proinflammatory cytokine with a wide range of biological activities. We determined the distribution of IL-1 beta following percutaneous transluminal coronary angioplasty (PTCA) of porcine arteries, and the presence of caspase-1 (required for the activation of IL-1 beta).


METHODS
Oversized balloon angioplasty was performed in Yorkshire White pigs and the vessels excised at selected intervals (1, 6, 18 h, 3, 7, and 14 days) post-PTCA. IL-1 beta and caspase-1 were then identified using reverse transcription polymerase chain reaction (RT-PCR), in situ RT-PCR, and immunohistochemistry.


RESULTS
IL-1 beta protein was detected in the inflammatory infiltrate up to 3 days after PTCA. Luminal endothelial cells contained IL-1 beta at 1 h, with peak expression at 3-7 days. Adventitial capillaries were IL-1 beta-positive at all timepoints. IL-1 beta was detected in adventitial cells at 3 days, with reduced levels at 7 and 14 days. At 7 days, neointimal cells were also IL-1 beta positive. No IL-1 beta was detected in non-PTCA control arteries. RT-PCR demonstrated IL-1 beta mRNA expression to be induced at 1 h, and absent at 3 days. In situ RT-PCR revealed this expression to be distributed throughout the arterial layers at 6 h, but localized to the adventitia at 18 h, with a baseline expression in the adventitial layer of non-PTCA controls. Caspase-1 was detected in luminal endothelial cells from 6 h, in adventitial cells from 3 days, and in neointimal cells from 7 days post-PTCA. This expression colocalized with IL-1 beta, indicating the potential for the IL-1 beta present to become activated.


CONCLUSIONS
We conclude that IL-1 beta is synthesised, in conjunction with caspase-1, by endothelial, inflammatory, and adventitial cells early (within 3 days) after PTCA, with decreased levels at later timepoints, suggesting that it has a key role to play in the early stages of healing following PTCA.
Chamberlain
J
J
Section of Medicine, University of Sheffield, Northern General Hospital, UK. j.chamberlain@sheffield.ac.uk
Gunn
J
J
Francis
S
S
Holt
C
C
Crossman
D
D
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D003327:Coronary Disease / Q000276:immunology / Q000628:therapy*; D003331:Coronary Vessels / Q000276:immunology / Q000293:injuries*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D013997:Time Factors; D014945:Wound Healing
D007375:Interleukin-1; D012333:RNA, Messenger; D020170:Caspase 1