Prevention of the post-chemotherapy relapse of tuberculous infection by combined immunotherapy

Prevention of the post-chemotherapy relapse of tuberculous infection by combined immunotherapy
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DOI:
10.1016/j.tube.2008.09.001
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发表时间:
2009-01-01
期刊:
影响因子:
3.2
通讯作者:
Dieli, Francesco
Dieli, Francesco
中科院分区:
医学4区
文献类型:
--
作者:
Buccheri, Simona;Reljic, Rajko;Dieli, Francesco

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我们报道了最近开发的一种联合免疫疗法(CIT),在用异烟肼和利福平进行4周的非消毒治疗后,能够防止在BALB/c、C57BI/6或C3H/HeJ小鼠的肺中复制结核杆菌的自发复发。以重组干扰素-γ、抗α-晶状单抗、IL-4中和多克隆抗体为代表的CIT方案。在感染后第5周,即化疗后第3周接种CIT时,最显著地减少了肺部活菌计数的8周复发。虽然CIT可显著提高肺肉芽肿面积、肺冲洗液中一氧化氮、细胞因子和趋化因子的水平,但这些与CIT对肺复发程度的有利作用并不直接相关。这些结果代表了一个原则证明,即所描述的CIT。当与化疗相结合时,可能会有潜力开发出一种更短的结核病治疗方案。(C)2008爱思唯尔有限公司。保留所有权利。
We report that a recently developed combined immunotherapy (CIT) has the capacity to prevent a spontaneous relapse of replicating Mycobacterium tuberculosis bacilli in the lungs of BALB/c, C57BI/6 or C3H/HeJ strains of mice, following 4 weeks of non-sterilising treatment with isoniazid and rifampicin. The CIT regimen, represented by recombinant IFN gamma, anti-alpha crystalline monoclonal IgA antibody and IL-4 neutralizing polyclonal antibody. reduced the 8-week relapse of viable bacterial Counts in the lungs most significantly, when CIT was inoculated during the 5th week post infection, i.e. during the 3rd week of chemotherapy. Although CIT enhanced lung granuloma area, nitric oxide, cytokine and chemokine levels in lung washings significantly, these could not be directly associated with the beneficial effect of CIT on the degree of relapse in the lungs. These results represent a proof-of-principle, that the described CIT. when combined with chemotherapy, could have potential for future development of a shorter regimen of tuberculosis treatment. (C) 2008 Elsevier Ltd. All rights reserved.