The antitumour activity of the interferon inducer bropirimine is partially mediated by endogenous tumour necrosis factor alpha.
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 alpha (TNF alpha) can also be an important mediator of the bropirimine antitumour effects. Increased serum levels of TNF alpha 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-TNF alpha serum just prior to drug treatment. These results indicate that bropirimine can induce the release of TNF alpha in vivo and that this endogenous TNF alpha may be important as far as the antitumour effect of the drug is concerned.
Scheringa
M
M
Laboratory for Experimental Surgery, Erasmus University, Rotterdam, The Netherlands.
IJzermans
J N
JN
Jeekel
J
J
Marquet
R L
RL
D000818:Animals; D000970:Antineoplastic Agents; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D003596:Cytosine; C033560:bropirimine