INTERLEUKIN-6 STIMULATES NEUTROPHIL PRODUCTION OF PLATELET-ACTIVATING-FACTOR

Interleukin-6 (IL-6) is an integral mediator of the acute phase respon se to injnry and infection; an exaggerated IL-6 response has been asso ciated with adverse clinical events. The precise role of IL-6 is uncle ar, but it appears capable of modulating the functional repertoire of mature neutrophils (PMNs). Our previous work demonstrated that IL-6-st imulated PMNs are primed by lower concentrations of platelet-activatin g factor (PAF) than nonstimulated PMNs. Recently, we have found that I L-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, an d PAF quantitated with a scintillation proximity assay. IL-6 (1 and 10 ng/ml) stimulated PMNs to produce increased quantities of PAF. PAF pr oduction was associated with an increase in PMN cytosolic calcium. The se data may provide mechanistic insight into IL-6 regulation of PMN-me diated cytotoxicity and the role of PAF in mediating IL-6 effects on P MNs.