CHICKEN INTERFERON TYPE-I AND TYPE-II ENHANCE SYNERGISTICALLY THE ANTIVIRAL STATE AND NITRIC-OXIDE SECRETION

This report shows that chicken type I and type II interferons (IFNs), like their mammalian counterparts, act synergistically such that a mix ture of the two has much greater activity than that expected from the separate contribution of each type. The degree of antiviral synergy wa s measured by virus plaque reduction and cytopathic effect (CPE) inhib ition in both primary and secondary chicken embryo cell cultures. Mixt ures of the two Ch-IFNs produced antiviral effects 3-10 times greater than that expected from strict additivity of each IFN acting alone. At high concentrations of IFN mixtures there was a qualitative shift to an exponential IFN action does-response curve that revealed synergisti c effects greater than 100-fold. Synergy resulted even with mixtures c ontaining less than 1 U/ml of either type of Ch-IFN, The antiviral eff ects developed more rapidly with mixtures than when type I or II Ch-IF N was used alone. Mixtures of the two types of Ch-IFN synergistically potentiated nitric oxide secretion in cells of the HD11 chicken macrop hage line. Molecular mechanisms are cited that may account for synergy between type I and type II IFNs, and speculation is offered on the ep idemiologic and therapeutic implications of synergy in vivo.