Interleukin 1 alpha (IL-1) and macrophage colony-stimulating factor (M-CSF) accelerate recovery from multiple drug-induced myelosuppression
Abstract
Interleukin 1 alpha (IL-1) and macrophage colony-stimulating factor (M-CSF) interact synergistically to enhance the restoration of stem and progenitor subpopulations in murine marrow and, vis-a-vis, to accelerate hematopoietic recovery in 5FU myelosuppressed mice. Similarly, IL-1 is reported to accelerate recovery following myelosuppressive treatment with doxorubicin (AdR), cis-platinum (DDP) and cyclophosphamide (CTx). Studies were carried out in C57Bl/6 mice in order to determine whether IL-1 (+/- M-CSF) intervention was as effective against the myelosuppression experienced following 5FU-based multiple drug combinations. Maximal-tolerated doses (MTD) of AdR (10 mg/kg), DDP (8 mg/kg) or CTx (250 mg/kg) were administered either alone or in combination with 150 mg/kg 5FU. Cytokine intervention (q24 hours x 2) was initiated 24 hours later. Hematopoietic recovery was assessed by measuring the femoral content of the more primitive [IL-1 + IL-3 + M-CSF-responsive] HPP-CFC and the total granulocyte levels in the animals over a ten-day interval following treatment. MTDs of AdR, DDP and CTx, when compared with 5FU, produced only marginal levels of myelosuppression. As a result, cytokine intervention in animals treated with AdR, DDP or CTx resulted in only a modest, transient increase in the HPP-CFC and total granulocyte subpopulations when compared with their effect on 5FU--treated animals. Neither AdR, DDP nor CTx interacted with 5FU to significantly increase the cytotoxic effects…
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