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High Blood Press Cardiovasc Prev 2008; 15 (3): 171-215 1120-9879/08/0003-0171/$48.00/0 © 2008 Adis Data Information BV. All rights reserved.

Atherosclerosis and Inflammation 1.4 Manidipine Inhibits the Release of Interleukin-6 (Il-6) Induced by Modified Lipoprotein and by TNF-Alpha in Culture Human Endothelial Cells S. Costa (1), M. Pedrelli (1), N. Ronda (2), M. Adorni (1), F. Bernini (1), G. Cremonesi (3) ` di Parma, Dipartimento Scienze Farmacologiche, Biol. e Chim. (1)Universita ` di Medicina Clinica Nefrologica Scienze Applicate, Parma, Italy, (2)Universita della Prevenzione, Parma, Italy, (3)Chiesi Farmaceutici S.p.A., Parma, Italy Introduction. The vascular inflammation is a critical event in the formation of atherosclerotic lesions. The exposure of endothelial cells to oxidized lipoproteins or other stress like hypertension, induce the expression of pro-atherogenic cytokines including interleukin-6 (IL-6). Drugs act by targeting one of the many factors involved in these processes can have direct antiatherosclerotic effect enhancing the beneficial effect of a reduction of cardiovascular risk factors such as high cholesterol level and hypertension. Aim. In this study we assessed t he ability of a lipophilic calcium antagonist Manidipine to reduce the release of IL-6 induced by modified lipoprotein or tumour necrosis factor-α (TNF-alpha) in human endothelial cells. Methods. The endothelial cells isolated from human umbilical vein (HUVEC) were incubate d with acetylated LDL (AcLDL) 50 μg/ml or oxidized LDL (OxLDL) 100 μg/ml or with TNF-alpha 2 ng/ml, and treated with Manidipine 1-20 μM for 48 hours. The release of IL-6 in the media was determined by ELISA analysis. Results. Our results showed that both AcLDL and OxLDL stimulate the secretion of IL-6 by 100% and 134% respectively. Treatment of cells with Manidipine 1 μM reduces the secretion of IL-6 from 211.6 ± 11.5 pg/ml to 122.4 ± 11.8 pg/ml (p

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