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  • Title: Prevention of the hematopoietic toxicity associated with zidovudine in vivo with IL-1 alone or in combination with GM-CSF administered to normal mice.
    Author: Gallicchio VS, Hughes NK, Tse KF, Gaines H.
    Journal: Growth Factors; 1993; 9(3):177-83. PubMed ID: 8274295.
    Abstract:
    We studied the effect of interleukin-1 (IL-1 alpha) either alone or administered with GM-CSF on the induction of hematopoietic toxicity associated with zidovudine (AZT) in vivo, as determined by peripheral blood indices, and assays of hematopoietic progenitors, i.e., erythroid (BFU-E), myeloid (CFU-GM), and megakaryocyte (CFU-Meg) cultured from bone marrow and spleen. Previous results reported from this laboratory have established dose-escalation of zidovudine to normal mice induced a dose-dependent decrease in hematocrit, WBC, and platelets with altered populations of marrow and splenic erythroid, myeloid and megakaryocyte progenitors. Daily administration of IL-1 alpha (recombinant murine, 5 u/animal) with or without GM-CSF (recombinant murine (10 micrograms/kg/bw) was associated with reduced AZT-toxicity as measured by increases in peripheral blood indices and progenitor stem cells, i.e., CFU-GM, CFU-Meg and BFU-E cultured from either bone marrow and spleen. The presence of GM-CSF amplified the effect observed with IL-1 especially with respect to myelopoiesis. These results demonstrate IL-1 with or without GM-CSF reverses AZT-hematopoietic toxicity when used in vivo.
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