Interleukin-6 stimulates neutrophil production of platelet-activating factor

Interleukin-6 (IL-6) is an integral mediator of the acute phase response to injnry and infection; an exaggerated IL-6 response has been associated with adverse clinical events. The precise role of IL-6 is unclear, but it appears capable of modulating the functional repertoire of mature neutrophils (PMNs). Our previous work demonstrated that IL-6-stimulated PMNs are primed by lower concentrations of platelet-activating factor (PAF) than nonstimulated PMNs. Recently, we have found that IL-6 suppresses PMN apoptosis via a PAF-like mechanism. We hypothesized that IL-6 stimulates PMNs to produce PAF. PMNs isolated from healthy human donors were incubated with IL-6 (0.1-100 ng/ml) at 37 degrees C. Lipid production was measured by use of thin-layer chromatography, and PAF quantitated with a scintillation proximity assay. IL-6 (1 and 10 ng/ml) stimulated PMNs to produce increased quantities of PAF. PAF production was associated with an increase in PMN cytosolic calcium. These data may provide mechanistic insight into IL-6 regulation of PMN-mediated cytotoxicity and the role of PAF in mediating IL-6 effects on PMNs.