Stem cell responses in myelosuppressed mice following sequential treatment with recombinant human interleukin 1 (rHuIL‐1), recombinant murine interleukin 3 (rMuIL‐3) and recombinant human macrophage colony‐stimulating factor (rHuM‐CSF)

Kovacs, C. J.; Harrell, J.P.; Evans, Mark J.; Abernathy, Reed S.; C, Roberts; Johnke, Roberta M.

doi:10.1002/stem.5530120117

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…However, our investigations were limited to the clarification of the in vitro effect of M-CSF. The presumed ability of M-CSF to induce the proliferation or differentiation of stromal cells in vivo might explain why M-CSF synergized with IL-1 to enhance the recovery of neutrophils and hematopoietic progenitor cells in myelosuppressed mice (Kovacs et al, 1992). In the present study, therefore, we examined the in vivo effect of M-CSF on the expansion of M-CSF-dependent SICs.…”

Section: Cd45mentioning

confidence: 94%

“…Recent studies revealed that M-CSF also enhances the effector functions of mature monocytes/macrophages such as cytokine production, chemotaxis, and tumoricidal activities (Suzu et al, 1989;Hashimoto et al, 1996;Douzono et al, 1995;Kimura et al, 1996;Morita et al, 1996). A number of studies concerning the in vivo effect of M-CSF on hematopoiesis have also been performed (Williams et al, 1987;Chikkappa et al, 1989;Kovacs et al, 1992). For instance, Kovacs et al (1992) showed that M-CSF synergized with interleukin-1 (IL-1) to promote the recovery of hematopoiesis in myelosuppressed mice.…”

Section: Cd45mentioning

confidence: 96%

“…A number of studies concerning the in vivo effect of M-CSF on hematopoiesis have also been performed (Williams et al, 1987;Chikkappa et al, 1989;Kovacs et al, 1992). For instance, Kovacs et al (1992) showed that M-CSF synergized with interleukin-1 (IL-1) to promote the recovery of hematopoiesis in myelosuppressed mice.…”

Section: Cd45mentioning

confidence: 96%

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In vivo stimulatory effect of macrophage colony-stimulating factor on the number of stroma-initiating cells

et al. 1999

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The in vivo effect of human macrophage colony-stimulating factor (M-CSF) on the number of cells that formed stromal colonies in an in vitro culture system (stroma-initiating cells; SICs) was investigated. We found that the number of SICs in the femurs of C57BL/6 mice was significantly increased by the treatment with M-CSF. We also found that the SICs were resistant to at least three different chemotherapeutic reagents, 5-fluorouracil (5-FU), cytarabine, and cyclophosphamide, because the femoral cells of mice treated with these reagents contained higher numbers of SICs than those of untreated mice. M-CSF treatment also increased the number of SICs of the reagent-pretreated mice. The SICs detected in our culture system were present only in Mac-1(-)CD45(-) cells, and the M-CSF treatment of 5-FU-pretreated mice actually increased the number of Mac-1(-)CD45(-) SICs. The Mac-1(-)CD45(-) SICs collected from mice that were pretreated with 5-FU and then treated with M-CSF formed stromal colonies under in vitro culture conditions that did not contain M-CSF but did contain a high concentration of fetal calf serum. This result suggested that SICs collected following the treatment procedure did not necessarily require the presence of M-CSF for their in vitro proliferation. Our study indicated that M-CSF has the ability to increase the number of progenitor or precursor cells for bone marrow stromal cells in vivo system.

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Section: Cd45mentioning

confidence: 94%

Section: Cd45mentioning

confidence: 96%

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In vivo stimulatory effect of macrophage colony-stimulating factor on the number of stroma-initiating cells

et al. 1999

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Enhanced Platelet Recovery in Myelosuppressed Mice Treated with Interleukin-1 and Macrophage Colony-Stimulating Factor: Potential Interactions with Cytokines Having Megakaryocyte Colony-Stimulating Activity

Kovacs¹,

Powell²,

Evans³

et al. 1996

Journal of Interferon & Cytokine Research

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Studies were carried out to determine whether the combination of IL-1 + M-CSF, similar to the effect of these cytokines on neutropenia, was able to reduce the duration of thrombocytopenia in the 5-fluorouracil (5-FU)-myelosuppressed mouse. In addition, comparisons were made between the in vivo effects of IL-1 + M-CSF and other "thrombopoietic" cytokines (e.g., IL-3, IL-6, and GM-CSF) that demonstrate some form of megakaryocytopoietic activity in vitro. Of the five cytokines studied, only IL-1 and IL-6, by themselves, were able to effect thrombopoietic recovery in the myelosuppressed mouse. IL-1, either when acting alone or interacting synergistically with M-CSF, was able to reduce significantly the period of thrombocytopenia, but the effects of IL-6 were restricted to enhancing platelet production during the period of rebound thrombocytopenia without altering the kinetics of thrombopoietic recovery. Moreover, none of the cytokine combinations studied were found to interact to reduce further the duration of thrombocytopenia beyond that observed with IL-1 + M-CSF. Nonetheless, IL-3, IL-6, and, to a lesser extent, GM-CSF were each able to interact with IL-1 + M-CSF to extend further the period of enhanced platelet production in the animal. However, scheduling studies suggested that these thrombopoietic cytokines interacted in sequence, rather than in concert, with IL-1 + M-CSF to enhance platelet production during thrombopoietic recovery. Furthermore, the data presented are consistent with the hypothesis that IL-1 + M-CSF initially acts on a multilineage, 5-FU-resistant target cell and that IL-6 (and possibly IL-3 and GM-CSF) serves as a secondary cytokine further to enhance platelet production during rebound thrombopoiesis in the 5-FU-treated mouse.

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Secondary Cytokines Interact in Sequence with Interleukin-1α (IL-1α) With or Without Macrophage Colony-Stimulating Factor (M-CSF) to Further Accelerate Granulopoietic Recovery in Myelosuppressed Animals

Kovacs¹,

Evans²,

Daly³

et al. 1997

Journal of Interferon & Cytokine Research

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Interleukin-1alpha (IL-1), by itself, accelerates both granulopoietic and thrombopoietic recovery in the 5-fluorouracil (5-FU) myelosuppressed mouse (FUM). As a primary cytokine, IL-1 also interacts in concert with macrophage colony-stimulating factor (M-CSF) to synergistically enhance hematopoietic recovery in the FUM. As part of our continuing interest in cytokine sequencing, studies were carried out to determine whether the addition of several secondary cytokines (GM-CSF, IL-3, and IL-6) to IL-1 (+/-M-CSF) would further enhance the stimulatory effects of the primary cytokine(s) on hematopoietic recovery in FUM. Throughout these studies, IL-1 (+/-M-CSF) was administered for 2 days to the FUM, and the secondary cytokines were given either in concert (days 1 and 2) or in sequence (days 3-6) or both with the primary cytokine(s). Based on the magnitude of 7-day post-5-FU granulocyte recovery, the results demonstrated that the synergistic effects of IL-1 + M-CSF treatment on granulopoietic recovery in FUM could not be duplicated by substituting either IL-3, IL-6, or GM-CSF for M-CSF. Nonetheless, the secondary cytokines were observed to enhance the stimulatory effects of IL-1 under the following administration schedules: (1) 2 days of IL-1, followed by a sequential treatment (days 3-6) with either IL-3 or IL-6, (2) 2 days of IL-1 + GM-CSF followed by an additional 4 days of GM-CSF alone, and (3) 2 days of IL-1 + GM-CSF followed by 3-4 days of a combination of GM-CSF and either IL-3 or IL-6. Although these cytokine treatment schedules led to an enhanced granulocyte recovery (vs. IL-1 alone) in FUM, the day 7 granulocyte numbers never exceeded those observed after 2 days of IL-1 + M-CSF. Similarly, granulocyte recovery in FUM receiving 2 days of IL-1 + M-CSF followed by either GM-CSF or IL-3 also was significantly greater than that observed with IL-1 + M-CSF alone. In contrast, however, the sequential administration of IL-6 with IL-1 + M-CSF, unlike IL-1, failed to further enhance granulopoietic recovery, suggesting that there may be an antagonism between IL-6 and M-CSF in the FUM. In summary, therefore, the secondary cytokines were found to interact more effectively when they were administered in sequence, rather than in concert, with both IL-1 and IL-1 + M-CSF.

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Stem cell responses in myelosuppressed mice following sequential treatment with recombinant human interleukin 1 (rHuIL‐1), recombinant murine interleukin 3 (rMuIL‐3) and recombinant human macrophage colony‐stimulating factor (rHuM‐CSF)

Cited by 5 publications

References 20 publications

In vivo stimulatory effect of macrophage colony-stimulating factor on the number of stroma-initiating cells

In vivo stimulatory effect of macrophage colony-stimulating factor on the number of stroma-initiating cells

Enhanced Platelet Recovery in Myelosuppressed Mice Treated with Interleukin-1 and Macrophage Colony-Stimulating Factor: Potential Interactions with Cytokines Having Megakaryocyte Colony-Stimulating Activity

Secondary Cytokines Interact in Sequence with Interleukin-1α (IL-1α) With or Without Macrophage Colony-Stimulating Factor (M-CSF) to Further Accelerate Granulopoietic Recovery in Myelosuppressed Animals

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