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 greater-than-or-equal-to 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 vims 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.