Scadden D T, Levine J D, Bresnahan J, Gere J, McGrath J, Wang Z, Resta D J, Young D, Hammer S M
Division of Hematology/Oncology, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
AIDS Res Hum Retroviruses. 1995 Jun;11(6):731-40. doi: 10.1089/aid.1995.11.731.
To determine the safety, tolerance, and hematological and virological effects of the recombinant hematopoietic growth factor interleukin 3 (IL-3) in HIV-1-infected individuals with cytopenia.
A phase I single-center trial was conducted with patients in cohorts of three receiving one of four dose levels of self-administered, subcutaneously injected IL-3 (0.5, 1.0, 2.5, or 5.0 micrograms/kg/day). Toxicities, hematological effects, and virological effects were recorded. Viral studies included serum HIV p24 antigen levels, quantitative plasma and peripheral blood mononuclear cell cultures, and quantitative, competitive polymerase chain reaction of patient plasma.
Increases in white blood cell counts (WBC) and absolute neutrophil counts (ANC) were noted at the higher dose levels while absolute eosinophil counts (AEC) increased in all patients. The percent changes in WBC from baseline ranged from 52 to 309 and in ANC from 20 to 262 in the 2.5- and 5.0-micrograms/kg/day groups. The mean AEC change was 17-fold (range, 2- to 59-fold). Hemoglobin, hematocrit, platelets, and CD4 and CD8 counts were generally unaffected although individual patients demonstrated increases in hemoglobin and platelet levels. Toxicities were generally mild, but one patient developed a transient local erythematous rash at the sites of IL-3 injection which pathologically demonstrated hypersensitivity vasculitis. Of note, viral studies did not demonstrate any consistent changes in HIV-1 activity.
These data demonstrate limited hematological effects of IL-3 monotherapy in HIV-1-infected patients with cytopenia. However, should IL-3 be incorporated into combination cytokine therapies for HIV disease, these data suggest that IL-3 does not enhance in vivo HIV-1 activity.
确定重组造血生长因子白细胞介素3（IL-3）对感染人类免疫缺陷病毒1型（HIV-1）且伴有血细胞减少的个体的安全性、耐受性以及血液学和病毒学影响。
进行了一项I期单中心试验，患者分为三个队列，每组三人，分别接受四种剂量水平之一的自我皮下注射IL-3（0.5、1.0、2.5或5.0微克/千克/天）。记录毒性反应、血液学影响和病毒学影响。病毒学研究包括血清HIV p24抗原水平、定量血浆和外周血单个核细胞培养，以及患者血浆的定量竞争性聚合酶链反应。
在较高剂量水平时，白细胞计数（WBC）和绝对中性粒细胞计数（ANC）增加，而所有患者的绝对嗜酸性粒细胞计数（AEC）均增加。在2.5微克/千克/天和5.0微克/千克/天组中，WBC较基线的百分比变化范围为52至309，ANC为20至262。AEC的平均变化为17倍（范围为2至59倍）。血红蛋白、血细胞比容、血小板以及CD4和CD8计数一般未受影响，尽管个别患者的血红蛋白和血小板水平有所升高。毒性反应一般较轻，但有一名患者在IL-3注射部位出现短暂的局部红斑皮疹，病理显示为过敏性血管炎。值得注意的是，病毒学研究未显示HIV-1活性有任何一致的变化。
这些数据表明IL-3单一疗法对感染HIV-1且伴有血细胞减少的患者的血液学影响有限。然而，如果将IL-3纳入HIV疾病的细胞因子联合治疗中，这些数据表明IL-3不会增强体内HIV-1活性。
