AUGMENTATION OF PRODUCTION OF TNF-ALPHA AND ANTITUMOR-ACTIVITY BY AN AMPHOTERICIN-B PREPARATION FOR CLINICAL USE IN MICE

Effects of amphotericin B on production of endogenous tumour necrosis factor alpha (TNF-alpha) and anti-tumour activity in mice was examined . Intravenous administration of Fungizone, an amphotericin B preparati on complexed with deoxycholate, augmented the induction of endogenous TNF in response to a second stimulus with intravenous doses of FK23 (h eat-killed Enterococcus faecalis). This augmentation was observed when more than 1.8 mu g of Fungizone was injected intravenously before int ravenous dosing of FK23. The time interval between priming injection o f Fungizone and secondary injection of FK23 for the maximal effect was 3 h. Similar augmentation of TNF production was also observed in amph otericin B-primed and FK23-injected mice. Correspondingly, anti-tumour activity of the combined, intravenous injection of Fungizone and FK23 with a 3-h interval was examined. Growth of Meth A fibrosarcoma was c learly inhibited by this combination but not by administration of eith er one alone. These results suggest that amphotericin B is able to eli cit anti-tumour activity, perhaps through activation of the immune sys tem, and in particular augmentation of the induction of endogenous TNF .