Padalko Elizaveta, Nuyens Dieter, De Palma Armando, Verbeken Erik, Aerts Joeri L, De Clercq Erik, Carmeliet Peter, Neyts Johan
Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Antimicrob Agents Chemother. 2004 Jan;48(1):267-74. doi: 10.1128/AAC.48.1.267-274.2004.
Viral replication, as well as an immunopathological component, is assumed to be involved in coxsackie B virus-induced myocarditis. We evaluated the efficacy of the interferon inducer Ampligen on coxsackie B3 virus-induced myocarditis in C3H/HeNHsd mice. The efficacy of Ampligen was compared with that of the interferon inducer poly(inosinic acid)-poly(cytidylic acid) [poly(IC)], alpha interferon 2b (INTRON A), and pegylated alpha interferon 2b (PEG-INTRON-alpha-2b). Ampligen at 20 mg/kg of body weight/day was able to reduce the severity of virus-induced myocarditis, as assessed by morphometric analysis, by 98% (P = 3.0 x 10(-8)). When poly(IC) was administered at 15 mg/kg/day, it reduced the severity of virus-induced myocarditis by 93% (P = 5.6 x 10(-5)). Alpha interferon 2b (1 x 10(5) U/day) and pegylated alpha interferon 2b (5 x 10(5) U/day) were less effective and reduced the severity of virus-induced myocarditis by 66% (P = 0.0009) and 78% (P = 0.0002), respectively. The observed efficacies of Ampligen and poly(IC) were corroborated by the observation that the drugs also markedly reduced the virus titers in the heart, as detected by (i) quantitative real-time reverse transcription-PCR and (ii) titration for infectious virus content. Whereas the electrocardiograms for untreated mice with myocarditis were severely disturbed, the electrocardiographic parameters were normalized in Ampligen- and poly(IC)-treated mice. Even when start of treatment with Ampligen was delayed until day 2 postinfection, a time at which lesions had already appeared in untreated control animals, a marked protective effect on the development of viral myocarditis (as assessed at day 6 postinfection) was still noted.
病毒复制以及免疫病理成分被认为与柯萨奇B病毒诱发的心肌炎有关。我们评估了干扰素诱导剂Ampligen对C3H/HeNHsd小鼠柯萨奇B3病毒诱发心肌炎的疗效。将Ampligen的疗效与干扰素诱导剂聚肌苷酸-聚胞苷酸[聚（IC）]、α干扰素2b（INTRON A）和聚乙二醇化α干扰素2b（PEG-INTRON-α-2b）的疗效进行了比较。通过形态计量分析评估，体重20mg/kg/天的Ampligen能够将病毒诱发心肌炎的严重程度降低98%（P = 3.0×10⁻⁸）。当以15mg/kg/天的剂量给予聚（IC）时，它将病毒诱发心肌炎的严重程度降低了93%（P = 5.6×10⁻⁵）。α干扰素2b（1×10⁵U/天）和聚乙二醇化α干扰素2b（5×10⁵U/天）效果较差，并分别将病毒诱发心肌炎的严重程度降低了66%（P = 0.0009）和78%（P = 0.0002）。Ampligen和聚（IC）的观察到的疗效通过以下观察得到证实：这些药物还显著降低了心脏中的病毒滴度，这通过（i）定量实时逆转录PCR和（ii）感染性病毒含量滴定检测到。虽然未治疗的心肌炎小鼠的心电图严重紊乱，但在接受Ampligen和聚（IC）治疗的小鼠中，心电图参数恢复正常。即使将Ampligen的治疗开始时间推迟到感染后第2天，此时未治疗的对照动物中已经出现病变，但对病毒性心肌炎的发展（在感染后第6天评估）仍有显著的保护作用。
