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ORIGINAL PAPER |
Division of Rheumatology, Allergy & Immunology, Winthrop University Hospital, Mineola, New York, USA; Department of Medicine, State University of New York at Stony Brook, New York, USA
Key Words. Dendritic cells • Cord blood • Interleukin 6 • Accessory cells • Hematopoiesis
Dr. Frances Santiago-Schwarz, Division of Rheumatology, Winthrop University Hospital, 222 Station Plaza North, Suite 430, Mineola, NY 11501, USA.
The aim of this study was to investigate the role of interleukin 6 (IL-6) in normal dendritic cell (DC) hematopoiesis. We used an enzyme-linked immunosorbent assay to quantitate IL-6 levels in CD34+ progenitor cell cultures favoring monocyte (mono) development versus those supporting mono-DC growth, and studied the neutralizing effects of
These studies substantiate the importance of IL-6 as a secondary cytokine during DC development and provide insight into another control point in the DC pathway.
IL-6 antibody on DC hematopoiesis. IL-6 levels in mono cultures (GM-CSF alone) were detected by day 4 and remained constant (~100 pg/ml) for 18 days. In mono-DC cultures, higher IL-6 levels correlated with DC content and development. Short-term mono-DC cultures initiated with GM-CSF + tumor necrosis factor (TNF) + stem cell factor (SCF) exhibited increases in IL-6 levels until day 11 (peak DC growth). By day 18, the levels had declined and cells expressing typical DC features were no longer present. Long-term mono-DC cultures sustained with GM-CSF + TNF + SCF contained the highest IL-6 levels (671 pg/ml) on day 11. In these cultures, DCs and higher IL-6 levels persisted beyond 18 days. Anti-IL-6 profoundly inhibited cell proliferation associated with DC hematopoiesis when added on days 0, 2 and 5 to GM-CSF + TNF + SCF cultures, indicating that various stages of mono-DC development rely on IL-6. There was no reduction in the T cell response when IL-6 was added to mixed leukocyte reaction cultures containing mature DCs as stimulators. Thus, IL-6 appears to downregulate developmental processes associated with optimal mono-DC growth, but not the effector functions of mature DCs.
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