High-yield interferon induction by 10-carboxymethyl-9-acridanone in mice and hamsters

Abstract

10-Carboxymethyl-9-acridanone (CMA) was shown to be a very potent interferon inducer in young and old Swiss albino as well as congenitally asplenic mice. This compound (molecular weight, 275) induced titers of interferon in plasma comparable to those obtained with the best viral inducers, attaining > 400,000 U/ml in mice in 2 to 3 h. CMA concentrations were highest in mouse plasma 1 h after intraperitoneal or oral delivery. Induction was dose dependent over a wide range. Intraperitoneal, subcutaneous, or intramuscular injections of CMA gave comparable ranges of interferon titers. Oral delivery by gavage gave lower titers (65,000 U/ml), but higher than those reported with other low-molecular-weight interferon inducers in mice. CMA injected into week-old hamsters (which usually produce iterferon poorly) induced levels of interferon as high as 6,400 U per ml of plasma in a dose-dependent fashion, but kinetics of interferon induction was less rapid than in mice. The mouse and hamster interferons induced by CMA had physical characteristics similar to those of virus-induced interferons of the homologous species. The unusually high yields of interferon obtainable with this chemical inducer suggest its use for further experimental antiviral or antitumor therapy.