Interleukin 6 is a permissive factor for monocytic colony formation by human hematopoietic progenitor cells

doi:10.1084/jem.175.4.1151

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Interleukin 6 is a permissive factor for monocytic colony formation by human hematopoietic progenitor cells

JH Jansen, JC Kluin-Nelemans, J Van Damme, GJ Wientjens, R Willemze and WE Fibbe
Department of Hematology, University Medical Center, Leiden, The Netherlands.

Since monocytes and macrophages that arise during the culture of bone marrow progenitor cells are potential sources of interleukin 6 (IL-6), we investigated whether auto- or paracrine production of this factor is involved in colony formation by normal hematopoietic progenitor cells. We added a polyclonal anti-IL-6 antiserum and a monoclonal anti-IL-6 antibody to cultures of monocyte- and T cell-depleted bone marrow cells. Colony formation was stimulated with granulocyte/monocyte-colony- stimulating factor (GM-CSF), monocyte-CSF, or IL-3. Addition of anti-IL- 6 antibody resulted in decreased numbers of monocytic colonies to 40- 50% of control values, whereas the numbers of granulocytic colonies were not altered. The inhibitory effect was preserved in cultures of CD34(+)-enriched bone marrow cells. As a second approach, we added a monoclonal antibody directed against the IL-6 receptor to cultures of monocyte- and T cell-depleted bone marrow cells. This antibody almost completely inhibited the growth of monocytic colonies, again without decreasing the number of granulocytic colonies. Finally, the importance of IL-6 in monocytopoiesis was demonstrated in serum-deprived bone marrow cultures: addition of exogenous IL-6 to cultures stimulated with GM-CSF resulted in increased numbers of monocytic colonies. Our results indicate that the permissive presence of IL-6 is required for optimal monocytic colony formation by bone marrow progenitor cells.
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