Reduced levels of TNF alpha in hypercholesterolemic individuals after treatment with pravastatin for 8 weeks

Background: cellular adhesion molecules (CAMs) expressed on the endothelial surface play a key role in the inflammatory process of atherosclerosis, an d increased expression of CAMs has been shown in hypercholesterolemic indiv iduals. The expression of CAMs is mediated by several cytokines including t umor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6). The aim of the present study was to assess the influence of pravastatin 40 mg per day on selected soluble CAMs; intercellular adhesion molecule I (ICAM-1), vasc ular cellular adhesion molecule I (VCAM-1), E-selectin, P-selectin and some circulating markers of inflammation, C-reactive protein (CRP) and the cyto kines TNF alpha and IL-6. 40 non-diabetic men, age below 70 years, with ser um total cholesterol 6-10 mmol/l combined with HDL-cholesterol less than or equal to1.2 mmol/l were included. The study was randomized, double blinded , placebo controlled, cross over designed with 8 weeks intervention periods . Fasting blood samples were drawn after 8 and 16 weeks. Results (median va lues): significant reduction of total cholesterol was achieved after treatm ent with pravastatin (7.8 on placebo vs. 5.7 mmol/l on pravastatin). TNFa w as significantly reduced after treatment with pravastatin (1.33 on placebo vs. 1.10 pg/ml on pravastatin, P = 0.032), whereas no differences in the le vels of the measured sCAMs, CRP and IL-6 were found. Subgroup analysis amon g smokers versus non-smokers showed a significant reduction in the level of TNF alpha only among the smokers. Conclusion: hypercholesterolemic individ uals treated with pravastatin 40 mg per day for 8 weeks showed a statistica lly significant reduction in the levels of TNF alpha as compared with place bo. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.