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.