EFFECTS OF FENOFIBRATE ON PLASMA CYTOKINE CONCENTRATIONS IN PATIENTS WITH ATHEROSCLEROSIS AND HYPERLIPOPROTEINEMIA IIB

Background and objective: In recent studies atherosclerosis has often been referred to as immune disease. The atherosclerotic plaque consist s of large amounts of inflammatory cells, mainly monocytes/macrophages and T lymphocytes. Macrophages activated by low-density lipoproteins (LDL) secrete tumor necrosis factor alpha (TNF-alpha) and interleukin- 1 (IL-1) in vitro, while LDL-stimulated T lymphocytes release interfer on gamma (IFN-gamma). The aim of this study was to estimate the plasma levels of TNF-alpha, IL-1, IFN-gamma in patients with hyperlipoprotei nemia IIb (HLPIIb) and atherosclerosis. Since the fibrates are drugs o f choice in HLPIIb, we additionally evaluated the effect of fibrates o n the cytokine levels. Methods: Ten patients with HLPIIb were treated with micronized fenofibrate for 1 month. Before and after treatment, t he cytokine levels were measured by the ELISA method. To accurately ev aluate cytokine levels, we excluded atherosclerotic patients and contr ol subjects with any inflammatory disease. Results: The initial Lipid parameters were as follows: total cholesterol (TC): 6.9 +/- 0.24 mmol/ l, triglycerides (TG): 3.44 +/- 0.53 mmol/l, LDL: 4.35 +/- 0.12 mmol/l , and apolipoprotein B (ApoB): 1.62 +/- 0.05 g/l. After 1 month of fen ofibrate treatment the parameters decreased to the following values: T C 5.36 +/- 0.42 mmol/l (p < 0.05), TG 1.94 +/- 0.30 mmol/l (p < 0.05), ApoB 1.43 +/- 0.04 g/l (p < 0.01), and LDL 3.75 +/- 0.34 mmol/l (p > 0.05). Before therapy, TNF-alpha levels in atherosclerotic patients we re higher than in control subjects, 19.2 +/- 1.6 and 9.9 +/- 1.1 pg/ml , respectively (p < 0.01). After 1-month therapy, TNF-alpha levels in atherosclerotic patients were 9.2 +/- 1.0 pg/ml (p < 0.01). Similarly, the initial levels of IFN-gamma were higher in atherosclerotic patien ts compared with healthy subjects, 44.4 +/- 5.3, and 19.4 +/- 2.1 pg/m l, respectively (p < 0.01). After fenofibrate therapy, IFN-gamma level s decreased to 24.8 +/- 2.9 pg/ml (p < 0.01). The decreased levels of TC, TG, and LDL correlated with the decreased levels of TNF-alpha and IFN-gamma. Conclusion: The results of this study indicate that plasma TNF-alpha and IFN-gamma levels in hyperlipidemic patients are higher t han in healthy subjects, and that fenofibrate is effective in decreasi ng lipids and cytokines in plasma.