Swindells S, Baldwin T, Kelly C, Baca-Regen L, Loomis L, Post D, Brichacek B, Stevenson M, Dominguez E A, Reddy R, Klein R, Liao M J, Testa D, McDonald T, Bellanti J, Skurkovich S, Gendelman H E
Department of Medicine, University of Nebraska Medical Center, Omaha, USA.
J Interferon Cytokine Res. 1996 Feb;16(2):127-37. doi: 10.1089/jir.1996.16.127.
To examine a possible association between plasma viremia and interferon-alpha (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN-alpha apheresis with two plasma volume exchanges was performed daily for 5 days. Clinical signs and symptoms and hematologic, virologic, and immunologic parameters were monitored. Two subjects developed anemia from phlebotomy, and one had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four subjects had a modest decrease in culturable plasma virus burden following the procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed its biologic and biochemical characterization. The HIV-1 IFN-alpha showed characteristics on ELISA, western blot, and biologic assays similar to two subspecies of the natural protein. The natural, recombinant, and HIV-1-induced IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN-alpha eluted from the column was not acid labile. The inability of large amounts of plasma IFN-alpha found in some patients with AIDS to affect viral burden likely reflects properties of the virus or of host factors independent of IFN-alpha.
为了研究获得性免疫缺陷综合征(AIDS)患者血浆病毒血症与α干扰素(IFN-α)之间可能存在的关联,我们对4名内源性血浆IFN-α水平持续升高的AIDS志愿者进行了单采血浆免疫吸附法(IFN-α单采血浆术)。每天进行2次血浆置换的IFN-α单采血浆术,共进行5天。监测临床症状和体征以及血液学、病毒学和免疫学参数。2名受试者因静脉穿刺出现贫血,1名受试者发生了与导管相关的菌血症。IFN-α单采血浆术仅能短暂去除IFN-α:IFN-α的清除仅导致其迅速重新生成。细胞相关的HIV-1没有变化,但4名受试者中有3名在该操作后可培养的血浆病毒载量略有下降。通过单采血浆术回收体内与HIV-1相关的IFN-α,使其能够进行生物学和生化特性分析。HIV-1 IFN-α在ELISA、免疫印迹和生物学检测中表现出与天然蛋白的两个亚型相似的特性。天然、重组和HIV-1诱导的IFN-α表现出几乎相同的抗病毒活性。从柱上洗脱的HIV-1 IFN-α对酸不敏感。一些AIDS患者中发现的大量血浆IFN-α无法影响病毒载量,这可能反映了病毒或与IFN-α无关的宿主因素的特性。