Gallicchio V S, Hughes N K, Tse K F, Gaines H
Division of Hematology/Oncology, University of Kentucky Medical Center, Lexington 40536-0084.
Life Sci. 1994;54(20):PL351-61. doi: 10.1016/0024-3205(94)90023-x.
Use of the anti-viral drug zidovudine in the treatment of acquired immunodeficiency syndrome (AIDS) has been associated with the development of hematopoietic toxicity. Several hematopoietic growth factors have been investigated in their ability to modulate such toxicity; however, no single factor has been demonstrated to produce restoration of hematopoiesis following use with zidovudine. We report results describing the effect of combination interleukin-1 (IL-1) and erythropoietin (Epo) in their ability to modulate the hematopoietic toxicity associated with dose-escalation zidovudine administered in normal mice. When administered over a six-week period, IL-1 and Epo raised the packed red cell volume, white blood cell and platelet counts in control mice and mice receiving dose-escalation zidovudine. These effects were attributed in part to the ability of combination IL-1 and Epo to increase erythroid, myeloid and megakaryocyte progenitor stem cells from bone marrow and spleen. These results indicate that use of combined IL-1 and Epo may be efficacious in ameliorating the hematopoietic toxicity associated with the use of zidovudine.
抗病毒药物齐多夫定用于治疗获得性免疫缺陷综合征(艾滋病)时,与造血毒性的发生有关。人们已经研究了几种造血生长因子调节这种毒性的能力;然而,尚未证明单一因子在与齐多夫定联合使用后能使造血功能恢复。我们报告了有关白细胞介素-1(IL-1)和促红细胞生成素(Epo)联合使用对正常小鼠中因剂量递增的齐多夫定所致造血毒性调节作用的研究结果。当在六周时间内给药时,IL-1和Epo提高了对照小鼠以及接受剂量递增齐多夫定的小鼠的红细胞压积、白细胞和血小板计数。这些作用部分归因于IL-1和Epo联合使用能够增加来自骨髓和脾脏的红系、髓系和巨核系祖干细胞。这些结果表明,联合使用IL-1和Epo可能有效改善与使用齐多夫定相关的造血毒性。