CONSENSUS INTERFERON INDUCES PEAK MESSENGER-RNA ACCUMULATION AT LOWERCONCENTRATIONS THAN INTERFERON-ALPHA-2A

The biological activity of a novel recombinant interferon, r-metIFN-co n1, which represents a consensus sequence of the most commonly appeari ng amino acids at each locus of 14 naturally occurring IFN-alphas, was assessed and compared to that of IFN-alpha2a. The increase in cellula r mRNA levels for three IFN-inducible genes served as a quantitative m easure of the effectiveness of the stimulation by each of the IFNs. Th ree cell lines were treated with equimolar amounts of two IFNs encompa ssing a 5 log range and mRNA was extracted al five different times aft er treatment. In all cases, r-metIFN-con1 produced mRNA increases at l ower concentrations than IFN-alpha2a. HLA-DRalpha mRNA, which is not a ffected by IFN-alpha in ME180 or Daudi cells, was also not affected by r-metIFN-con1. However, in Eskol cells, both IFNs effected an increas e in HLA-DRalpha mRNA to similar levels. The r-metIFN-con1 was effecti ve at approximately 10-fold lower molar concentrations. At effective c oncentrations (10-fold lower molar dose of r-metIFN-con1), both IFNs p roduced similar kinetics of accumulation of all three mRNAs tested. r- metIFN-con1 is therefore more effective than IFN-alpha2a at the level of mRNA regulation as well as the antiviral and antiproliferative acti vities that have been reported previously.