Comparation interferon- inducing and antiviral properties of 2-amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166), tilorone hydrochloride, and polyinosinic-polycytidylic acid

Abstract

2-Amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166), polyinosinic acid-polycytidylic acid [poly(I:C)], and tilorone HCl induced high levels of serum interferon in mice. Each consequently protected mice against infection with several viruses. After daily injection of inducer, mice developed a reduced interferon response (hyporeactivity) to each compound. However, hyporeactivity developed more slowly to U-25,166 and poly(I:C) than to tilorone HCl. After onset of hyporeactivity, 5 to 6 days without each inducer were required before normal serum interferon levels could be stimulated. Animals also developed a hyporeactive state as a consequence of Semliki Forest or encephalomyocarditis virus infections. By day 2 of either infection, mice had a suppressed interferon response to tilorone HCl, but remains responsive to poly(I:C) or U-25,166 until day 4. In vivo, poly(I:C) stimulated interferon production in a variety of cells and organs, whereas the tilorone HCl and U-25,166 responses involved a nonlymphoid component of the reticuloendothelial system. In vitro, poly(I:C) induced interferon in a variety of murine cells, U-25,166 was active in murine thymus and spleen organ cultures, and tilorone was inactive. These data indicate that U-25,166 is an interesting low-molecular-weight interferon inducer.