Interleukin-1β and tumor necrosis factor-α release in normal and diseased human infrarenal aortas

The presence of chronic inflammatory cells in the adventitia and media of abdominal aortic aneurysms and aortic occlusive disease suggest an immunologic response. The purpose of this study is to determine whether normal or diseased infrarenal aortas liberate the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Twenty-six infrarenal aortic biopsies (5 aortic occlusive disease, 15 abdominal aortic aneurysms, and 6 cadaveric donors) were weighed, minced into small pieces, and incubated in media for 48 hours. Conditioned media was harvested at 48 hours and assayed for IL-1β or TNF-α with use of an ELISA assay. Comparison of groups was performed with a one-way analysis of variance. The constitutive IL-1β produced by abdominal aortic aneurysms was significantly different than that in cadaveric donors (908 ± 194 pg/ml [SE] vs 100 ± 30 pg/ml). There was no statistically significant difference between abdominal aortic aneurysms and aortic occlusive disease (908 ± 194 pg/ml vs 604 ± 256 pg/ml) or aortic occlusive disease and cadaveric donor (604 ± 256 vs 100 ± 30). In time-course studies for the release of IL-1β, abdominal aortic aneurysms demonstrated maximal release at 48 hours. IL-1β release was augmented by lipopolysaccharide in all categories. A dose response curve demonstrated maximal IL-1β release on stimulation with 5 μg/ml LPS. Constitutive TNF-α production was low, ranging from 13 ± 1.5 pg/ml in cadaveric donor, to 20 pg/ml in aortic occlusive disease, and 24 ± 11 pg/ml in abdominal aortic aneurysms. There was no augmentation in TNF-α with lipopolysaccharide. These experiments demonstrate (1) A significant increase in the amount of constitutive IL-1β produced in abdominal aortic aneurysms as compared with cadaveric donor; (2) IL-1β secretion is not different between aortic occlusive disease and abdominal aortic aneurysms, nor aortic occlusive disease and cadaveric donor; (3) TNF-α production is similar in all cases. We suggest that the inflammatory infiltrate found in infrarenal aortic disease produces cytokines that may contribute to the pathogenesis of the underlying disease.