Gallicchio V S, Hughes N K, Tse K F, Gaines H
Department of Internal Medicine, Lucille P. Markey Cancer Center, University of Kentucky Medical Center, Lexington 40536-0084.
Growth Factors. 1993;9(3):177-83.
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.
我们研究了单独使用白细胞介素-1（IL-1α）或与粒细胞巨噬细胞集落刺激因子（GM-CSF）联合使用时，对体内齐多夫定（AZT）相关造血毒性的诱导作用，通过外周血指标以及对从骨髓和脾脏培养的造血祖细胞（即红系祖细胞（BFU-E）、髓系祖细胞（CFU-GM）和巨核细胞祖细胞（CFU-Meg））的检测来确定。本实验室先前报道的结果表明，对正常小鼠递增剂量给予齐多夫定会导致血细胞比容、白细胞和血小板呈剂量依赖性下降，同时骨髓和脾脏中的红系、髓系和巨核细胞祖细胞群体发生改变。每日给予IL-1α（重组鼠源，5单位/动物），无论是否联合GM-CSF（重组鼠源（10微克/千克体重）），均可使外周血指标和祖干细胞（即从骨髓和脾脏培养的CFU-GM、CFU-Meg和BFU-E）增加，从而降低AZT毒性。GM-CSF的存在增强了IL-1所观察到的效应，尤其是在髓系造血方面。这些结果表明，无论有无GM-CSF，IL-1在体内使用时均可逆转AZT的造血毒性。
