Prevention of viral myocarditis with recombinant human leukocyte interferon alpha A/D in a murine model.
Prevention of viral myocarditis with recombinant human leukocyte interferon alpha A/D in a murine model.
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DOI：
10.1016/s0735-1097(87)80472-2
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发表时间：
1987-06
影响因子：
24
通讯作者：
A. Matsumori;C. Crumpacker;W. Abelmann
中科院分区：
文献类型：
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作者：
A. Matsumori;C. Crumpacker;W. Abelmann
本文观察了重组人白细胞干扰素α A/D对实验性脑心肌炎病毒性心肌炎的作用。空斑减少试验表明，干扰素α A/D（9.7 U/ml）在感染脑心肌炎病毒前24小时给药，可抑制50%的人羊膜（FL）细胞体外空斑形成。将4周龄雄性DBA/2小鼠腹腔内接种10个空斑形成单位（pfu）的脑心肌炎病毒。在感染前1天开始皮下注射干扰素α A/D（组1，102 U/g体重/天，组2，103 U/g体重/天，组3，104 U/g体重/天）。第4组在同一天开始给药，第5组在病毒接种后1天给药（两组均为104 U/g/天）。对照组小鼠注射生理盐水。心肌病毒滴度实验3组（8.2 ± 25.2 × 102 pfu/mg）和实验4组（3.0 ± 5.5 × 103 pfu/mg）均显著低于对照组（5.6 ± 4.1 × 104 pfu/mg）。组织学检查显示，所有对照组小鼠均出现广泛的心肌坏死和细胞浸润，但第3组无心肌坏死或细胞浸润，第4组坏死和浸润程度较轻。对照组小鼠心肌病毒滴度和组织学变化与1、2、5组无显著差异。因此，在病毒接种前或同时给予干扰素α A/D，可有效抑制病毒复制，减轻病毒性心肌炎模型的炎症反应和心肌损伤。
Effects of recombinant human leukocyte interferon α A/D on experimental myocarditis due to encephalomyocarditis virus were investigated. Plaque reduction assays revealed that 50% of plaque formation in vitro in human amnion (FL) cells was inhibited by interferon α A/D (9.7 U/ml) when it was administered 24 hours before infection with the encephalomyocarditis virus. Four week old male DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units (pfu) of encephalomyocarditis virus. Interferon α A/D was administered subcutaneously (102U/g body weight per day in Group 1, 103U/g per day in Group 2 and 104U/g per day in Group 3) starting 1 day before infection. It was also administered starting the same day in Group 4 and 1 day after virus inoculation in Group 5 (104U/g per day in both groups). Control mice were injected with saline solution. Each group consisted of 10 mice; they were killed on day 4 for evaluation.Myocardial virus titers were significantly lower in Group 3 (8.2 ± 25.2 × 102pfu/mg, p < 0.05) and Group 4 (3.0 ± 5.5 × 103pfu/mg, p < 0.05) than in control mice (5.6 ± 4.1 × 104pfu/mg). Histologic examination showed extensive myocardial necrosis and cellular infiltration in all control mice, but no myocardial necrosis or cellular infiltration in Group 3 and less severe necrosis and infiltration in Group 4. There were no significant differences in myocardial virus titers or histologic changes between control mice and Group 1, 2 or 5.Thus, interferon α A/D, when administered starting before or simultaneously with virus inoculation, effectively inhibited myocardial virus replication and reduced the inflammatory response and myocardial damage in an experimental model of viral myocarditis.