Immunoglobulin treatment ameliorates murine myocarditis associated with reduction of neurohumoral activity and improvement of extracellular matrix change

Immunoglobulin treatment ameliorates murine myocarditis associated with reduction of neurohumoral activity and improvement of extracellular matrix change
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DOI:
10.1016/s0735-1097(00)00978-5
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发表时间:
2000-11-15
影响因子:
24
通讯作者:
Ochiai, H
Ochiai, H
中科院分区:
医学1区
文献类型:
--
作者:
Kishimoto, C;Takamatsu, N;Ochiai, H

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目的观察免疫球蛋白对非人致病性脑心肌炎病毒所致小鼠心肌炎的治疗作用,并分析治疗前后血浆细胞因子和儿茶酚胺水平及细胞外基质的变化。然而,目前还不能确定免疫球蛋白对心肌炎的有益作用是由于抗病毒作用还是其他未知的作用。方法体外测定人免疫球蛋白(Polylobin-N)对脑心肌炎病毒的抗病毒活性。免疫球蛋白(1g/kg/d)给感染病毒的小鼠每日一次,连续两周,从实验一开始同时接种病毒,实验二在接种病毒后第14天开始给药。结果空斑减数法体外检测不到免疫球蛋白的抗病毒活性。体内实验表明,免疫球蛋白治疗可通过降低血浆儿茶酚胺、干扰素-α和可溶性细胞间黏附分子-1的水平,减轻实验1中伴有间质纤维蛋白沉积的心肌坏死和实验2中通过降低血浆儿茶酚胺、干扰素-α和可溶性细胞间黏附分子-1而改善的心肌重塑的间质纤维化。结论免疫球蛋白治疗可通过降低神经体液活性来抑制与细胞外基质改变相关的心肌炎。(C)2000年由美国心脏病学会颁发。
OBJECTIVES We examined effects of immunoglobulin on murine myocarditis induced by encephalomyocarditis virus, not pathogenic to humans, and analyzed the plasma cytokine and catecholamine levels and the changes of the extracellular matrix with or without the treatment.BACKGROUND We have previously shown that immunoglobulin therapy suppressed murine coxsackievirus B3 myocarditis by an antiviral effect. However, it is not yet determined whether beneficial effects of immunoglobulin for myocarditis are due to antiviral effects or to other unknown effects.METHODS Antiviral activity of human immunoglobulin (Polyglobin-N) against encephalomyocarditis virus was determined in vitro. Immunoglobulin (1 g/kg/day) was administered intraperitoneally to the virus-infected mice daily for two weeks, beginning simultaneously with virus inoculation in experiment I and on day 14 after virus inoculation in experiment II.RESULTS Antiviral activity of immunoglobulin could not be detected in the assay of a plaque-reduction method in vitro. The in vivo study showed that immunoglobulin administration ameliorated both myocardial necrosis with interstitial fibrin deposition in experiment I and interstitial fibrosis with the improvement of ventricular remodeling in experiment II by the reduction of plasma catecholamines, interferon-alpha, and soluble intercellular adhesion molecule-1.CONCLUSIONS Immunoglobulin therapy could suppress myocarditis associated with the improvement of extracellular matrix changes by the reduction of neurohumoral activity. (C) 2000 by the American College of Cardiology.