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Blood. 1988 Jun;71(6):1759-63.

Synergism between interleukin-6 and interleukin-3 in supporting proliferation of human hematopoietic stem cells: comparison with interleukin-1 alpha.

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  • 1VA Medical Center, Charleston, SC.

Abstract

Currently available evidence suggests that in the steady state, the majority of hematopoietic stem cells are dormant in cell cycle and reside in the so-called G0 period. Studies in our laboratory indicated that once a stem cell leaves G0, its subsequent proliferation requires the presence of interleukin-3 (IL-3). Recently it was reported that interleukin-1 (IL-1) may stimulate stem cells to become sensitive to IL-3. In a separate study, we observed that interleukin-6 (IL-6, also known as B cell stimulatory factor-2/interferon beta 2) possesses synergism with IL-3, shortening the G0 period of murine hematopoietic stem cells. We report here that human IL-6 and IL-3 act synergistically in support of the proliferation of progenitors for human blast cell colonies and that IL-1 alpha reveals no synergism with IL-3 when tested against purified human marrow progenitors. Panned My-10+ human marrow cells were plated in culture and on day 14 of incubation, either IL-3, IL-6, IL-1 alpha or a combination of these factors was added to the cultures. Blast cell colony formation was analyzed daily between days 18 and 32 of culture. IL-6 or IL-1 alpha alone failed to support blast cell colony formation. In the presence of IL-3 alone, blast cell colonies continued to emerge between days 21 and 27. When a combination of IL-3 and IL-6 was added, blast cell colonies developed earlier than in cultures with IL-3 alone and twice as many blast cell colonies were identified. IL-1 alpha failed to augment IL-3-dependent blast cell colony formation. Replating studies of the individual blast cell colonies revealed various types of single as well as multilineage colonies. These observations suggest that IL-6 shortens the G0 period of human hematopoietic stem cells and that the reported synergistic activities of IL-1 on primitive hematopoietic cells may be indirect.

PMID:
3259443
[PubMed - indexed for MEDLINE]
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