251. Recruitment of primitive peripheral blood cells: synergism of interleukin 12 with interleukin 6 and stem cell factor.
- Author
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Grafte-Faure S, Leveque C, Vasse M, Soria C, and Vannier JP
- Subjects
- Antigens, CD34, Cell Differentiation physiology, Culture Media, Serum-Free, Drug Synergism, Fluorouracil pharmacology, Humans, Receptors, Interleukin-6 metabolism, Stem Cell Factor, Hematopoietic Stem Cells cytology, Interleukin-12 pharmacology, Interleukin-6 pharmacology
- Abstract
Interleukin-12 (IL-12), a heterodimeric cytokine with potent biological activity, was evaluated for effects on proliferation of human immature progenitor cells in vitro. In vitro proliferation of 5-FU-resistant CD34+ (G0) peripheral blood stem cells (PBSC) in response to sequential cytokine stimulation was examined in the presence and absence of 100 ng/ml IL-12. PBSC were found to include a subpopulation of cells that were resistant to 25 microg/ml 5-FU and required a combination of IL-12, IL-6 and SCF for the production of morphologically recognizable clonogenic elements at day 14 in semisolid medium. Furthermore, addition of IL-6 soluble receptor (IL-6Rs) to IL-6 and SCF led to a similar recruitment. We also demonstrated a significant production of IL-6Rs by CD34+ cells stimulated by IL-12. We noted that glucocorticoids and aldosterone, a mineralocorticoid, had a positive effect on recruitment, but neither mineralocorticoid nor glucocorticoids induced IL-6Rs production by CD34+ cells. The recruitment mechanism by steroids seemed to be different from that used by IL-12. These results confirm previous findings which showed the involvement of IL-12 on immature PBSCs and suggest that IL-12 might play a key role in early haemopoiesis.
- Published
- 1999