Consensus interferon induces peak mRNA accumulation at lower concentrations than interferon-alpha 2a

Abstract

The biological activity of a novel recombinant interferon, r-metIFN-con1, which represents a consensus sequence of the most commonly appearing amino acids at each locus of 14 naturally occurring IFN-alpha s, was assessed and compared to that of IFN-alpha 2a. The increase in cellular mRNA levels for three IFN-inducible genes served as a quantitative measure of the effectiveness of the stimulation by each of the IFNs. Three cell lines were treated with equimolar amounts of two IFNs encompassing a 5 log range and mRNA was extracted at five different times after treatment. In all cases, r-metIFN-con1 produced mRNA increases at lower concentrations than IFN-alpha 2a. HLA-DR alpha mRNA, which is not affected by IFN-alpha in ME180 or Daudi cells, was also not affected by r-metIFN-con1. However, in Eskol cells, both IFNs effected an increase in HLA-DR alpha mRNA to similar levels. The r-metIFN-con1 was effective at approximately 10-fold lower molar concentrations. At effective concentrations (10-fold lower molar dose of r-metIFN-con1), both IFNs produced similar kinetics of accumulation of all three mRNAs tested. r-metIFN-con1 is therefore more effective than IFN-alpha 2a at the level of mRNA regulation as well as the antiviral and antiproliferative activities that have been reported previously.