Cyclic AMP metabolism and interferon induction in mice after treatment with 10-carboxymethyl-9-acridanone

The low molecular weight substance 10-carboxymethyl-9-acridanone (CMA) is capable to induce interferon (IFN) production. In order to determine the effect of CMA on cyclic AMP alterations in relation to IFN production, male ABD2F1 hybrid mice were orally treated with several concentrations of CMA (400, 600 and 800 mg/kg) for varying periods of time up to 24 hr. IFN titres were detected as early as 3 and 4 hr, respectively, in mouse plasma after CMA administration, and their production continued for at least 24 hr. Maximum IFN titres were assayed in the presence of 800 mg/kg (3,200 IU/ml) CMA. Measuring of the intracellular concentrations of cyclic AMP in thymus and spleen revealed that in early stage (0.5 to 2 hr) CMA exhibited a dose dependent increase. The drug acted as an inhibitor of low Km cAMP phosphodiesterase in cell homogenates; a significantly enhanced enzyme activity (1 to 4 hr) was found after exposure to CMA in vivo.