ENHANCED PRODUCTION OF THE CHEMOTACTIC CYTOKINES INTERLEUKIN-8 AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN HUMAN ABDOMINAL AORTIC-ANEURYSMS

Inflammatory leukocytes play a central role in the pathogenesis of hum an atherosclerotic disease, from early atherogenesis to the late stage s of atherosclerosis, such as aneurysm formation. We have shown previo usly that human abdominal aortic aneurysms are characterized by the pr esence of numerous chronic inflammatory cells throughout the vessel wa ll (Am J Pathol 1990,137:1199-1213). The signals that attract lymphocy tes and monocytes into the aortic wall in aneurysmal disease remain to be precisely defined. We have studied the production of the chemotact ic cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein -1 (MCP-1) by aortic tissues obtained from 47 subjects. We compared th e antigenic production of these cytokines by explants of: 1) human abd ominal aneurysmal tissue, 2) occlusive (atherosclerotic) aortas, and 3 ) normal aortas. IL-8, which is chemotactic for neutrophils, lymphocyt es, and endothelial cells was liberated in greater quantities by abdom inal aortic aneurysms than by occlusive or normal aortas. Using immuno histochemistry, macrophages, and to a lesser degree endothelial cells, were found to be positive for the expression of antigenic IL-8. Simil arly, MCP-1, a potent chemotactic cytokine for monocytes/macrophages, was released by explants from abdominal aortic aneurysms in greater qu antities than by explants from occlusive or normal aortas. Using immun ohistochemistry, the predominant MCP-1 antigen-positive cells were mac rophages and to a lesser extent smooth muscle cells. Our results indic ate that human abdominal aortic aneurysms produce IL-8 and MCP-1, both of which may serve to recruit additional inflammatory cells into the abdominal aortic wall, hence perpetuating the inflammatory reaction th at may result in the pathology of vessel wall destruction and aortic a neurysm formation.