Interferon counteracts pyrimidinone-induced hyporeactivity and the combined treatment has antitumor effect in mice.

Abstract

A potent interferon (IFN) inducer, 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP), induced hyporeactivity in mice, and so IFN induced by subsequently administered ABPP was reduced even 120 hr after the first administration of ABPP. This hyporeactivity was counteracted by the injection of IFN (10,000 IU or more) 3 hr before the subsequent administrations of ABPP. Since the injection of more than 5,000 IU/mouse of IFN 3 hr before an administration of ABPP enhanced the circulating IFN titer, the priming effect in vivo by IFN may result in the reduction of hyporeactivity. Administrations of ABPP (200 mg/kg or 500 mg/kg) at intervals of 2 days and the injection of IFN (25,000 IU/mouse) 3 hr before each administration of ABPP to neuroblastoma-bearing A/J mice reduced the mortality and completely cured 40% of the mice in each combined therapy group. These results suggest that the combined use of the IFN inducer with IFN may be available for patients with neoplasm or viral infection.