Interleukin-6 exacerbates early atherosclerosis in mice
Interleukin-6 exacerbates early atherosclerosis in mice
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DOI：
10.1161/01.atv.19.10.2364
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发表时间：
1999-10-01
影响因子：
8.7
通讯作者：
Tracy, R
中科院分区：
文献类型：
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作者：
Huber, SA;Sakkinen, P;Tracy, R
急性时相蛋白，响应全身促炎细胞因子，如白细胞介素-6，在心血管疾病中升高，是未来缺血事件的预测标志物，甚至在几十年内。这表明促炎细胞因子和/或急性期蛋白在早期病变发展中的作用。为了探索这个问题，我们喂养C57 Bl/6和非肥胖糖尿病雄性小鼠高脂肪（20%总脂肪，1.5%胆固醇）饮食和ApoE缺陷雄性小鼠高脂肪和正常饮食6至21周，每周注射5000 U重组白细胞介素-6（rIL-6）或生理盐水缓冲液。当动物被安乐死时收集血液，并测定细胞因子、急性期蛋白和胆固醇。在所有小鼠中，IL-6注射导致促炎细胞因子（IL-6，4.6倍; IL-1 β，1.6倍;和组织坏死因子-α，1.7倍）和纤维蛋白原（1.2倍）显著增加，血浆中白蛋白浓度降低（0.9倍）。总胆固醇水平在rIL-6治疗组和未治疗组之间没有变化。通过主动脉窦的连续切片用油红O染色以检测脂肪条纹，并通过图像分析确定病变的面积。尽管在有或没有rIL-6治疗的非肥胖糖尿病小鼠中没有检测到脂肪条纹，但rIL-6治疗使C57 Bl/6和ApoE缺陷小鼠的病变大小增加了盐水治疗动物病变的1.9至5.1倍。这些结果表明，在适当的情况下，循环促炎细胞因子和急性时相蛋白的变化可能不仅仅是动脉粥样硬化的标志物，但在早期病变发展的实际参与者。
Acute-phase proteins, which respond to systemic proinflammatory cytokines such as interleuken-6, are elevated in cardiovascular disease and are predictive markers of future ischemic events, even over decades. This suggests a role for proinflammatory cytokines and/or acute phase proteins in early lesion development. To explore this issue, we fed C57Bl/6 and nonobese diabetic male mice high-fat (20% total fat, 1.5% cholesterol) diets and ApoE-deficient male mice both high-fat and normal chow diets for 6 to 21 weeks, injecting them weekly with either 5000 U recombinant interleukin-6 (rIL-6) or saline buffer. Blood was collected when animals were euthanized and assayed for cytokines, acute-phase proteins, and cholesterol. Across all mice, IL-6 injection resulted in significant increases in proinflammatory cytokines (IL-6, 4.6-fold; IL-1 beta, 1.6-fold; and tissue necrosis factor-alpha, 1.7-fold) and fibrinogen (1.2-fold) and with decreased concentrations of albumin (0.9-fold) in plasma. Total cholesterol levels were unchanged between rIL-6-treated and nontreated groups. Serial sections through the aortic sinus were stained with oil red O to detect fatty streaks, and area of the lesions was determined by image analysis. Although no fatty streaks were detected in the nonobese diabetic mice with or without rIL-6 treatment, rIL-6 treatment increased lesion size in C57Bl/6 and ApoE-deficient mice 1.9- to 5.1-fold over lesions in saline-treated animals. These results suggest that under the appropriate circumstances changes in circulating proinflammatory cytokines and acute-phase proteins may be more than just markers of atherosclerosis but actual participants in early lesion development.