Effect of in vivo macrophage colony-stimulating factor on fungistasis of bronchoalveolar and peritoneal macrophages against Cryptococcus neoformans

Abstract

Macrophage colony-stimulating factor (M-CSF) given subcutaneously at a dose of 2.5 mg/kg of body weight (4.75 x 10(6) U/kg) to CD-1 male mice 8 to 12 weeks old was found to enhance significantly the fungistasis of bronchoalveolar macrophages (BAM) against Cryptococcus neoformans. When M-CSF was given 1, 3, 7, 9, or 13 days before an ex vivo challenge with C. neoformans, fungistasis was increased (P ranged from < 0.05 to < 0.001) compared with that induced by control BAM. A maximum effect was seen by days 1 and 3 after administration of M-CSF. Twenty-one days after M-CSF, BAM did not produce significantly enhanced fungistasis. M-CSF also significantly enhances the fungistatic effect of peritoneal macrophages (PM) if given 1, 3, and 7 days prior to testing against C. neoformans in comparison with control PM (P ranged from < 0.05 to < 0.001). PM did not produce enhanced fungistasis 9 or 13 days after administration of M-CSF. These studies demonstrating in vivo enhancement of anticryptococcal activity of macrophages with M-CSF provide a rationale for in vivo use of M-CSF to enhance resistance to infection with C. neoformans.