The interferon inducer ampligen [poly(I)-poly(C12U)] markedly protects mice against coxsackie B3 virus-induced myocarditis.
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.
Padalko
Elizaveta
E
Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Nuyens
Dieter
D
De Palma
Armando
A
Verbeken
Erik
E
Aerts
Joeri L
JL
De Clercq
Erik
E
Carmeliet
Peter
P
Neyts
Johan
J
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D002522:Chlorocebus aethiops; D003384:Coxsackievirus Infections / Q000517:prevention & control* / Q000821:virology*; D004562:Electrocardiography; D029822:Enterovirus B, Human; D006321:Heart / Q000821:virology; D007369:Interferon Inducers / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000473:pathology / Q000517:prevention & control* / Q000821:virology*; D009206:Myocardium / Q000473:pathology; D011070:Poly I-C / Q000627:therapeutic use*; D011072:Poly U / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014709:Vero Cells
D000998:Antiviral Agents; D007369:Interferon Inducers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011072:Poly U; C047490:poly(I).poly(c12,U); D011070:Poly I-C