INTERLEUKIN-6 AND INTERLEUKIN-8 PROTEIN AND GENE-EXPRESSION IN HUMAN ARTERIAL ATHEROSCLEROTIC WALL

Interleukin 6 (IL-6) and interleukin 8 (IL-8) are present in the human arterial atherosclerotic wall as cellular and extracellular deposits in the connective tissue matrix. Quantitative determinations of IL-6 b y ELISA showed mean values of 27.6 +/- 3.3 ng/100 mg protein in normal intima, 37.3 +/- 2.1 ng/100 mg protein in fibrous plaque and 25.7 +/- 4.3 ng/100 mg total extracted protein in media. IL-8 levels were 3.5 +/- 0.6 ng/100 mg protein in normal intima, 11.3 +/- 2.1 ng/100 mg pro tein in fibrous plaque and 8.5 +/- 1.4 ng/100 mg total extracted prote in in media. Fibrous plaques presented statistically significant highe r levels of both IL-6 and IL-8. IL-6 and IL-8 gene transcripts were pr esent in human iliac fibrous plaque and media prelevated at surgery in dicating that a local production by the cells of the arterial wall par ticipate to their accumulation. We also tested the role of complement activation in induction of IL-6 and IL-8 protein synthesis as well as the subsequent activation of endothelial cells. Only IL-8 was induced by complement activation and this may contribute to increased IL-8 lev els found in the atherosclerotic wall. When exposed to terminal comple ment complexes, endothelial cells in culture also showed an increase o f both DNA-synthesis and p70 S6 kinase activity indicating that comple ment is able to induce not only IL-8 synthesis but also cell activatio n. The presence of IL-6 and IL-8 in the arterial wall where complement activation also occurred, clearly show the involvement of inflammator y events in initiation and progression of atherosclerosis.