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.