Endogenously produced interleukin 6 is an accessory cytokine for dendritic cell hematopoiesis.
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 alphaIL-6 antibody on DC hematopoiesis. IL6 levels in mono cultures (GM-CSF alone) were detected by day 4 and remained constant (approximately 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 level 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 alphaIL-6 was added to mixed leukocyte reaction cultures containing mature DCs as stimulators. Thus, alphaIL-6 appears to downregulate developmental processes associated with optimal mono-DC growth, but not the effector functions of mature DCs. 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.
Santiago-Schwarz
F
F
Division of Rheumatology, Allergy & Immunology, Winthrop University Hospital, Mineola, New York 11501, USA.
Tucci
J
J
Carsons
S E
SE
D000906:Antibodies / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology*; D005312:Fetal Blood; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000502:physiology*; D008858:Microscopy, Phase-Contrast
D000906:Antibodies; D015850:Interleukin-6