EX-VIVO EFFECTS OF MACROPHAGE-COLONY-STIMULATING FACTOR ON HUMAN MONOCYTE ACTIVITY AGAINST FUNGAL AND BACTERIAL PATHOGENS

The ex vivo effects of macrophage colony-stimulating factor (M-CSF) on antifungal and antibacterial activities of human elutriated monocytes were studied. Cells were isolated prior to the initiation of therapy, on day 3 and at week 7, in six patients with an advanced malignancy r eceiving M-CSF in a phase I study, Superoxide anion production by mono cytes in response to N-formyl methionyl leucyl phenylalanine was enhan ced at day 3 of therapy (P = 0.011). In addition, at day 3, fungicidal activity against blastoconidia of Candida albicans was enhanced by M- CSF treatment (P = 0.026), whereas antifungal activity against hyphae of Aspergillus fumigatus was not significantly changed. Bactericidal a ctivity against Staphylococcus aureus was increased at day 3 (P = 0.00 4). By Northern blot analysis, M-CSF does not upregulate the expressio n of components of the NADPH-oxidase, the multicomponent enzyme system responsible for generation of superoxide radicals by monocytes. Inste ad, the predominant effect of M-CSF on circulating monocytes is probab ly a post-transcriptional effect. In conclusion, these findings sugges t that administration of M-CSF to patients may enhance microbicidal ac tivities and thus may provide a useful adjunct to conventional antimic robial therapy. (C) 1996 Academic Press Limited