RECOMBINANT INTERFERON-BETA AND INTERFERON-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 interf erons (IFN-alpha 2a, IFN-beta, and IFN-gamma) in cultured human myocar dial fibroblasts to select a candidate for trial in heart disease indu ced by cardiotropic enterovirus, e.g., coxsackievirus B3 (CVB3). Cells were exposed to CVB3, and after 7 days, when a persistent infection h ad developed, IFN was added. Virus yields were measured on alternate d ays for the next 7 or 16 days, and IFN activity was assessed as the pe rcentage reduction in yield. IFN-gamma and IFN-beta were both highly a ctive 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 25 0 IU/ml of either IFN, no infectious virus was formed. Unexpectedly, I FN-alpha 2a (EC(99) > 1250 IU/ml) was at least 120 times less active t han IFN-beta; after use for 8 days or more, the minor effects it produ ced were no longer related to the concentration applied. Despite the p harmacokinetic advantages of IFN-alpha 2a, our data suggest that IFN-b eta should in preference be evaluated in the clinic.