The antitumour activity of the interferon inducer bropirimine is partially mediated by endogenous tumour necrosis factor α

Pyrimidinones, like 2-amino-5-bromo-6-phenyl-4-pyrimidinone (bropirimine), are potent immunomodulators. Natural killer cell activity and macrophage cytotoxicity are increased after bropirimine treatment, an effect exerted through induction of cytokines. Up to now, the interferons have been supposed to be the main mediators but we have found that tumour necrosis factor α (TNFα) can also be an important mediator of the bropirimine antitumour effects. Increased serum levels of TNFα were seen in rats after intraperitoneal administration of 200 mg/kg bropirimine on 2 consecutive days. We also found that the tumour-growth-inhibiting effect of the drug on a colon carcinoma in rats could be reduced about 40% by giving the rats rabbit anti-TNFα serum just prior to drug treatment. These results indicate that bropirimine can induce the release of TNFα in vivo and that this endogenous TNFα may be important as far as the antitumour effect of the drug is concerned.