Synergistic Interaction of Interferon-β and Interferon-γ in Coxsackievirus B3-Infected Carrier Cultures of Human Myocardial Fibroblasts

Synergistic Interaction of Interferon-β and Interferon-γ in Coxsackievirus B3-Infected Carrier Cultures of Human Myocardial Fibroblasts
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DOI:
10.1093/infdis/166.5.985
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发表时间:
1992-11
期刊:
The Journal of Infectious Diseases
影响因子:
--
通讯作者:
A. Heim;A. Canu;P. Kirschner;T. Simon;G. Mall;P. Hofschneider;R. Kandolf
A. Heim;A. Canu;P. Kirschner;T. Simon;G. Mall;P. Hofschneider;R. Kandolf
中科院分区:
其他
文献类型:
--
作者:
A. Heim;A. Canu;P. Kirschner;T. Simon;G. Mall;P. Hofschneider;R. Kandolf

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在持续感染柯萨奇病毒B3的人心肌成纤维细胞载体培养物中研究了人干扰素-β(IFN-β)和人重组干扰素-γ(rIFN-γ)的抗病毒作用,持续时间为21天。在低至30 IU IFN-β +10 IU rIFN-γ/mL的浓度下观察到协同作用,通过定量原位杂交测定,平均病毒滴度从6.0 x 10(7)降至1.3 x 10(4)pfu/mL,感染细胞数从14.4%降至0.1%。较高浓度的干扰素(均>或= 30 IU/mL)与短暂的拮抗作用相关,随后是抗病毒协同作用。使用100 IU的IFN-β加30 IU的rIFN-γ/mL,在停止IFN应用后持续达到并持续6周消除感染性病毒,而使用单一药物需要至少3倍的浓度。总之,我们的数据支持低剂量IFN组合方案的概念,这可能有助于治疗肠道病毒性心脏病。
The antiviral effects of human interferon-beta (IFN-beta) and human recombinant interferon-gamma (rIFN-gamma) were studied in persistently coxsackievirus B3-infected carrier cultures of human myocardial fibroblasts over a period of 21 days. Synergism was observed with concentrations as low as 30 IU of IFN-beta plus 10 IU of rIFN-gamma/mL, reducing mean viral titers from 6.0 x 10(7) to 1.3 x 10(4) pfu/mL and number of infected cells from 14.4% to 0.1% as determined by quantitative in situ hybridization. Higher concentrations of IFNs (both > or = 30 IU/mL) were associated with transient antagonism followed by antiviral synergism. With 100 IU of IFN-beta plus 30 IU of rIFN-gamma/mL, elimination of infectious virus was consistently achieved and sustained for 6 weeks after cessation of IFN application, whereas at least threefold higher concentrations were required with single drugs. In summary, our data support a concept of low-dose IFN combination schedules that might become useful in the treatment of enteroviral heart disease.