Low-dose interferon-alpha accelerates atherosclerosis in an LDL receptor-deficient mouse model.
Low-dose interferon-alpha accelerates atherosclerosis in an LDL receptor-deficient mouse model.
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DOI：
10.1016/j.ejim.2003.08.010
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发表时间：
2003-12-01
影响因子：
8
通讯作者：
Harats, Dror
中科院分区：
文献类型：
--
作者：
Levy, Zohar;Rachmani, Rita;Harats, Dror
背景：大量证据表明动脉粥样硬化与免疫反应有关。斑块中大多数活化的T细胞是辅助性T细胞1亚型（Th 1），其分泌干扰素-γ（IFN-γ），现在通常被认为是促动脉粥样硬化的细胞因子。已发现干扰素-α（IFN-α）抑制IL-12和IFN-γ的分泌并增加IL-10的产生。因此，它可能具有抗动脉粥样硬化作用。本研究的目的是阐明IFN-α在转基因小鼠动脉粥样硬化模型中对动脉粥样硬化形成的作用。方法：将8周龄低密度脂蛋白受体（LDL）缺陷小鼠随机分为治疗组和对照组，每组13只。治疗组每隔一天腹腔注射1000单位IFN-α，持续5周，对照组小鼠接受0.9%NaCl。这些老鼠被喂食西方饮食。结果：IFN-α治疗组和对照组小鼠的体重增加相似（分别为3.9+/-1.0 g vs. 3.4+/-1.8 g）。IFN-α治疗显著增加了治疗组和未治疗组小鼠的血浆胆固醇水平（平均值分别为31.03+/-5.53 mmol/l vs. 24.91+/-6.03 mmol/l; p
Background: Solid evidence suggests that atheroscleosis is associated with immune reactions. Most of the activated T cells in the plaque are T helper 1 subtype (Th1), which secrete interferon-gamma (IFN-gamma), now generally accepted as a proatherogenic cytokine. Interferon-alpha (IFN-alpha) has been found to inhibit the secretion of IL-12 and IFN-gamma and to increase IL-10 production. It may, therefore, be atheroprotective. The aim of the present study was to clarify the effect of IFN-alpha on atherogenesis in a transgenic mouse model of atherosclerosis. Methods: 8-week-old low-density lipoprotein (LDL) receptor-deficient mice were allocated randomly into treatment and control groups (n=13 each). The treatment group received 1000 units of IFN-alpha i.p. every other day for 5 weeks and the control mice received 0.9% NaCl. The mice were fed a Western diet. Results: The IFN-alpha-treated and the control mice showed a similar weight gain (mean 3.9+/-1.0 g vs. 3.4+/-1.8 g, respectively). Treatment with IFN-alpha significantly increased the plasma cholesterol levels in both treated and untreated mice (mean 31.03+/-5.53 mmol/l vs. 24.91+/-6.03 mmol/l, respectively; p