Madej A, Okopien B, Kowalski J, Zielinski M, Wysocki J, Szygula B, Kalina Z, Herman Z S
Department of Clinical Pharmacology, Silesian Medical University, Katowice, Poland.
Int J Clin Pharmacol Ther. 1998 Jun;36(6):345-9.
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.
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.
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.
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.
在最近的研究中，动脉粥样硬化常被视为一种免疫疾病。动脉粥样硬化斑块由大量炎症细胞组成，主要是单核细胞/巨噬细胞和T淋巴细胞。体外实验中，被低密度脂蛋白（LDL）激活的巨噬细胞可分泌肿瘤坏死因子α（TNF-α）和白细胞介素-1（IL-1），而受LDL刺激的T淋巴细胞则释放干扰素γ（IFN-γ）。本研究旨在评估IIb型高脂蛋白血症（HLPIIb）合并动脉粥样硬化患者血浆中TNF-α、IL-1、IFN-γ的水平。鉴于贝特类药物是治疗HLPIIb的首选药物，我们还评估了贝特类药物对细胞因子水平的影响。
10例HLPIIb患者接受微粒化非诺贝特治疗1个月。治疗前后采用酶联免疫吸附测定（ELISA）法检测细胞因子水平。为准确评估细胞因子水平，我们排除了患有动脉粥样硬化的患者以及患有任何炎症性疾病的对照受试者。
初始血脂参数如下：总胆固醇（TC）：6.9±0.24 mmol/L，甘油三酯（TG）：3.44±0.53 mmol/L，低密度脂蛋白（LDL）：4.35±0.12 mmol/L，载脂蛋白B（ApoB）：1.62±0.05 g/L。非诺贝特治疗1个月后，这些参数降至以下值：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），LDL 3.75±0.34 mmol/L（p>0.05）。治疗前，动脉粥样硬化患者的TNF-α水平高于对照受试者，分别为19.2±1.6和9.9±1.1 pg/ml（p<0.01）。1个月治疗后，动脉粥样硬化患者的TNF-α水平为9.2±1.0 pg/ml（p<0.01）。同样，动脉粥样硬化患者的初始IFN-γ水平高于健康受试者，分别为44.4±5.3和19.4±2.1 pg/ml（p<0.01）。非诺贝特治疗后，IFN-γ水平降至至24.8±2.9 pg/ml（p<0.01）。TC、TG和LDL水平的降低与TNF-α和IFN-γ水平的降低相关。
本研究结果表明，高脂血症患者血浆中的TNF-α和IFN-γ水平高于健康受试者，且非诺贝特可有效降低血浆中的血脂和细胞因子水平。
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