Interleukin-6 (IL-6) and low O-2 concentration (1%) synergize to improve the maintenance of hematopoietic stem cells (Pre-CFC)

Abstract

Low O-2 concentration (1%) favors the self-renewal of hematopoietic stem cells and inhibits committed progenitors (CFC). Since IL-6 influences both stem cells and committed progenitors at 20% O-2, we studied its effects in cultures at 1% O-2. The pre-CFC activity in Lin- population of mouse bone marrow was analyzed following 10 days of serum-free culture in medium (LCI) supplemented with IL-3 with and without IL-6, at 20 and 1% O-2 and phenotypic differentiation and proliferative history monitored. The IL-6 receptor expression and initiation of VEGF-A synthesis were also investigated. At 20% O-2, the effects of IL-6 on pre-CFC were negligible but effects on CFC were apparent; conversely, at 1% O-2, the IL-6 enhances activity of pre-CFC but not of CFC. Unlike at 20% O-2, at 1% O-2 a subpopulation of cells remained Lin- in spite of extensive proliferation. However, the absolute number of Lin- cells, did not correlate with pre-CFC activity. A relative increase in VEGF transcripts at 1% O-2 in presence of IL-3 alone was enhanced by the addition of IL-6. IL-6 enhanced pre-CFC activity at 1% O-2 and this was correlated to the induction of VEGF. These data reinforce the concept that physiologically low oxygenation of bone marrow is a regulator of stem cell maintenance. Since the 20% O-2 does not exist in tissues in vivo, further studies in vitro at lower O-2 concentrations should revise our knowledge relating to cytokine effects on stem and progenitor cells.