The interferon inducer ampligen [poly(I)-poly(C12U)] markedly protects mice against coxsackie B3 virus-induced myocarditis.

Abstract

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.

• Authors: Elizaveta Padalko, Dieter Nuyens, Armando De Palma, Erik Verbeken, Joeri L Aerts, Erik De Clercq, Peter Carmeliet, Johan Neyts
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 48 Issue 1 Pg. 267-74 (Jan 2004) ISSN: 0066-4804 [Print] United States
• PMID: 14693549 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferon Inducers
• Interferon alpha-2
• Interferon-alpha
• RNA, Viral
• Recombinant Proteins
• Poly U
• poly(I).poly(c12,U)
• Poly I-C

Topics

• Animals
• Antiviral Agents (therapeutic use)
• Chlorocebus aethiops
• Coxsackievirus Infections (prevention & control, virology)
• Electrocardiography
• Enterovirus B, Human
• Heart (virology)
• Interferon Inducers (therapeutic use)
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Male
• Mice
• Mice, Inbred C3H
• Myocarditis (pathology, prevention & control, virology)
• Myocardium (pathology)
• Poly I-C (therapeutic use)
• Poly U (therapeutic use)
• RNA, Viral (analysis, biosynthesis)
• Recombinant Proteins
• Reverse Transcriptase Polymerase Chain Reaction
• Vero Cells