Synergistic interaction of interferon-beta and interferon-gamma in coxsackievirus B3-infected carrier cultures of human myocardial fibroblasts.
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.
Heim
A
A
Department of Internal Medicine I, University of Munich, Federal Republic of Germany.
Canu
A
A
Kirschner
P
P
Simon
T
T
Mall
G
G
Hofschneider
P H
PH
Kandolf
R
R
D002478:Cells, Cultured; D015342:DNA Probes; D004357:Drug Synergism; D029822:Enterovirus B, Human / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D009206:Myocardium; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D014779:Virus Replication / Q000187:drug effects*
D015342:DNA Probes; D012367:RNA, Viral; D011994:Recombinant Proteins; D016899:Interferon-beta; D007371:Interferon-gamma