Reduction of macrophage-mediated tumor cytotoxicity by pretreatment with GM-CSF.

The effect of granulocyte/macrophage colony stimulating factor (GM-CSF) on macrophage activation by interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS) was studied in a murine model system. When peritoneal macrophages were pretreated with GM-CSF for 24 hrs, a strong reduction of IFN-gamma-induced tumor cytotoxicity and LPS-triggered tumor necrosis factor-alpha (TNF-alpha) release was found. In contrast, GM-CSF treatment of macrophages for only 4 to 8 hrs enhanced TNF-alpha production. These data suggest that GM-CSF may affect macrophage activation in a biphasic manner in that a time period of enhanced responsiveness to IFN-gamma is followed by a longlasting period of refractoriness.