Long term, high dose interferon-alpha treatment in HTLV-I-associated myelopathy/tropical spastic paraparesis: A combined clinical, virological and immunological study
Long term, high dose interferon-alpha treatment in HTLV-I-associated myelopathy/tropical spastic paraparesis: A combined clinical, virological and immunological study
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DOI：
10.1016/s0022-510x(96)05319-1
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发表时间：
1997-04-15
影响因子：
4.4
通讯作者：
Kobayashi, T
中科院分区：
文献类型：
--
作者：
Yamasaki, K;Kira, J;Kobayashi, T
在7例HTLV-I相关性脊髓病（HAM）/热带痉挛性轻瘫（TSP）患者中研究了长期、高剂量α-干扰素（IFN-α）治疗的疗效。IFN-α的给药剂量为6 × 10（6）国际单位，最初2周每天一次，此后每周3次，持续22周。5名患者在IFN-α治疗期间和治疗结束后6个月内表现出运动能力的持续改善。另一名对IFN-α有反应的患者最初因抑郁症在3个月时退出，而另一名患者首先恶化，随后退出。在6名应答者中，通过定量聚合酶链反应方法评估的携带HTLV-I基因组的外周血淋巴细胞（PBL）的绝对数量在治疗期间显著减少（减少28.6+/-16.6%，P=0.0083），而1名恶化患者显示HTLV-I感染细胞增加2.5倍。在完成长期IFN-α治疗的应答者中，即使在停止IFN-α治疗后，来自单细胞培养的CD 4（+）T克隆细胞的自身增殖也明显受到抑制。此外，所有患者治疗期间外周血CD 8（+）DR（+）T细胞和血清可溶性IL-2受体水平均显著升高（分别为P=0.0431和P=0.0041）。因此，我们的研究结果表明，HTLV-I前病毒DNA载量的减少和长期IFN-α治疗的免疫调节有助于其持续的临床益处。(C)1997年Elsevier Science B.V.
The efficacy of long-term, high dose interferon-alpha (IFN-alpha) therapy was studied in seven patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). IFN-alpha was administered at a dose of 6x10(6) international units daily for the initial 2 weeks and thereafter 3 times a week for the following 22 weeks. Five patients showed a sustained improvement in motor performance during and up to 6 months after the completion of IFN-alpha. The other patient who responded to IFN-alpha initially dropped out at 3 months because of depression, while another patient first deteriorated and thereafter dropped out. In the six responders, the absolute number of peripheral blood lymphocytes (PBL) harboring the HTLV-I genome as evaluated by the quantitative polymerase chain reaction method decreased significantly during the therapy period (28.6+/-16.6% reduction, P=0.0083), whereas the one deteriorated patient showed a 2.5-fold increase in HTLV-I-infected cells. The autoproliferation of CD4(+) T clone cells from a single cell culture was markedly depressed even after the cessation of IFN-alpha in the responders who completed long-term IFN-alpha therapy. In addition, the CD8(+)DR(+) T cells in the peripheral blood and soluble IL-2 receptor levels in the sera increased significantly during the therapy in all patients (P=0.0431 and P=0.0041, respectively). Therefore, the results of our study suggested that both the reduction of HTLV-I proviral DNA load and immunomodulation by long-term IFN-alpha therapy contributed to its sustained clinical benefits. (C) 1997 Elsevier Science B.V.