Recombinant Interferons beta and gamma have a higher antiviral activity than interferon-alpha in coxsackievirus B3-infected carrier state cultures of human myocardial fibroblasts.
We compared the antiviral activities of three recombinant human interferons (IFN-alph2a, IFN-beta, and IFN-gamma) in cultured human myocardial fibroblasts to select a candidate for trial in heart disease induced by cardiotropic enterovirus, e.g., coxsackievirus B3 (CVB3). Cells were exposed to CVB3, and after 7 days, when a persistent infection had developed, IFN was added. Virus yields were measured on alternate days for the next 7 or 16 days, and IFN activity was assessed as the percentage reduction in yield. IFN-gamma and IFN-beta were both highly active and reduced virus yields by 2 log (EC(99)) at concentrations of 23.4 IU/ml (SD = 8.6) and 10.1 IU/ml (SD = 3.2), respectively; with 250 IU/ml of either IFN, no infectious virus was formed. Unexpectedly, IFN-alpha2a (EC(99)> 1250 IU/ml) was at least 120 times less active than IFN-beta; after use for 8 days or more, the minor effects it produced were no longer related to the concentration applied. Despite the pharmacokinetic advantages of IFN-alpha2a, our data suggest that IFN-beta should in preference be evaluated in the clinic.
Heim
A
A
Institut fur Virologie und Seuchenhygiene, OE5230, Medizinische Hochschule Hannover, D-30623 Hannover, Germany.
Stille-Seigener
M
M
Pring-Akerblom
P
P
Grumbach
I
I
Brehm
C
C
Kreuzer
H
H
Figulla H-R
D000998:Antiviral Agents / Q000627:therapeutic use*; D002353:Carrier State; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000188:drug therapy*; D029822:Enterovirus B, Human / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D006321:Heart / Q000187:drug effects* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use*; D009206:Myocardium / Q000166:cytology; D011994:Recombinant Proteins / Q000627:therapeutic use
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016899:Interferon-beta; D007371:Interferon-gamma; D007372:Interferons