Effects of fenofibrate on plasma cytokine concentrations in patients with atherosclerosis and hyperlipoproteinemia IIb.
OBJECTIVE
In recent studies atherosclerosis has often been referred to as immune disease. The atherosclerotic plaque consists 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 interferon gamma (IFN-gamma). The aim of this study was to estimate the plasma levels of TNF-alpha, IL-1, IFN-gamma in patients with hyperlipoproteinemia IIb (HLPIIb) and atherosclerosis. Since the fibrates are drugs of choice in HLPIIb, we additionally evaluated the effect of fibrates on the cytokine levels.


METHODS
Ten patients with HLPIIb were treated with micronized fenofibrate for 1 month. Before and after treatment, the cytokine levels were measured by the ELISA method. To accurately evaluate cytokine levels, we excluded atherosclerotic patients and control 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 fenofibrate treatment the parameters decreased to the following values: TC 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 were 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 patients compared with healthy subjects, 44.4 +/- 5.3, and 19.4 +/- 2.1 pg/ml, respectively (p < 0.01). After fenofibrate therapy, IFN-gamma levels 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.


CONCLUSIONS
The results of this study indicate that plasma TNF-alpha and IFN-gamma levels in hyperlipidemic patients are higher than in healthy subjects, and that fenofibrate is effective in decreasing lipids and cytokines in plasma.
Madej
A
A
Department of Clinical Pharmacology, Silesian Medical University, Katowice, Poland.
Okopien
B
B
Kowalski
J
J
Zielinski
M
M
Wysocki
J
J
Szygula
B
B
Kalina
Z
Z
Herman
Z S
ZS
D000328:Adult; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood / Q000187:drug effects*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood / Q000187:drug effects; D007375:Interleukin-1 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D000960:Hypolipidemic Agents; D007375:Interleukin-1; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011345:Fenofibrate