Cytokines that activate proteolysis are increased in abdominal aortic aneurysms.

Abstract

Abdominal aortic aneurysm (AAA) disease is characterized by an increase in proteolysis and loss of matrix components. The cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), products of activated macrophages and T cells, are known to increase the production of matrix-degrading enzymes in some pathological states. Seven AAA and five control aortic tissue extracts were assayed for TNF-alpha and IL-1 beta with ELISA. TNF-alpha was elevated significantly in AAA extracts compared with controls (86 +/- 34 pg/mg of total protein versus 1 +/- 1 pg/mg of total protein; P < .001). IL-1 beta concentration also was significantly increased in the AAA specimens (48 +/- 14 pg/mg of total protein versus 12 +/- 5 pg/mg of total protein; P < .05). Immunoblotting demonstrated secreted forms of TNF-alpha in the AAA extracts, and possible membrane-bound forms were observed when the tissues were detergent-extracted. Known forms of IL-1 beta also were observed on immunoblots of AAA tissue extracts. The presence of TNF-alpha and IL-1 beta in AAA tissue underscores the importance of the infiltrating inflammatory cells present in the media and adventitia of aneurysmal aortic wall and further implicates an inflammatory process in the pathogenesis of AAA.