Interleukin-6 stimulates neutrophil production of platelet-activating factor.
Interleukin-6 (IL-6) is an integral mediator of the acute phase response to injury 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 increase 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.
Biffl
W L
WL
Department of Surgery, Denver General Hospital, CO 80204, USA.
Moore
E E
EE
Moore
F A
FA
Barnett
C C
CC
Silliman
C C
CC
Peterson
V M
VM
D000595:Amino Acid Sequence; D002118:Calcium / Q000097:blood; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical
D015850:Interleukin-6; D008055:Lipids; D010972:Platelet Activating Factor; D002118:Calcium