Prevention of the hematopoietic toxicity associated with zidovudine in vivo with IL-1 alone or in combination with GM-CSF administered to normal mice.
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.
Gallicchio
V S
VS
Department of Internal Medicine, Lucille P. Markey Cancer Center, University of Kentucky Medical Center, Lexington 40536-0084.
Hughes
N K
NK
Tse
K F
KF
Gaines
H
H
D000818:Animals; D004338:Drug Combinations; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006403:Hematologic Tests; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015215:Zidovudine / Q000037:antagonists & inhibitors / Q000633:toxicity*
D004338:Drug Combinations; D007375:Interleukin-1; D015215:Zidovudine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor