Effect of platelet-activating factor on monocyte activation and production of tumor necrosis factor

The effect of platelet-activating factor (PAF) or human peripheral-blood-derived monocytes (PBM) was examined. The addition of PAF to monocyte cultures did not activate the cells to mediate cytotoxicity activity against 51Cr-labeled target cells. Furthermore, supernatants derived from the treated cultures were not cytotoxic. However, these supernatants contained tumor necrosis factor (TNF) when assayed by a sensitive radioimmunoassay. Further kinetic studies indicated that cytotoxic supernatant is detected at 2-4 h following PAF treatment but not overnight treatment, suggesting, perhaps, the presence of inhibitors interfering with the cytotoxic activity. Cells pretreated with PAF responded poorly to a second stimulation with phorbol myristate acetate whereas a secondary response was seen with cells pretreated with interferon-gamma. These results suggest that PAF is involved in regulating cytokine production by monocytes and thus plays a role in the immune response to foreign antigens.