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通过细胞因子的肺特异性递送对小鼠空气传播性肺结核进行免疫治疗。

Immunotherapy of airborne tuberculosis in mice via the lung-specific delivery of cytokines.

作者信息

Denis M, Ghadirian E

机构信息

Unité de Recherche Pulmonaire, Centre Hospitalier de l'Université de Sherbrooke, Sherbrooke, Québec; and Montreal General Hospital Research Institute, Montreal, Quebec.

出版信息

Can J Infect Dis. 1993 Jan;4(1):38-42. doi: 10.1155/1993/954372.

DOI:10.1155/1993/954372
PMID:22346418
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3250802/
Abstract

The immunotherapeutic potential of interleukin-2 (IL-2), tumour necrosis factor alpha (TNFα) and interferon gamma (IFN-γ) administered by aerosol was examined on mice infected with Mycobacterium tuberculosis by the aerogenic route. Infection of balb/c mice with 10(4) colony forming units (cfu) of M tuberculosis led to death of all mice at day 35 post infection after progressive microbial growth in the lungs. Aerosolization of IL-2 (100 μg per mouse) did not promote an increase in resistance to tuberculosis, as seen by growth of M tuberculosis in the lungs. Administration of IFN-γ or TNFα (100 μg) by the aerosol route led to a significant reduction in microbial growth in the lungs and a 100% survival of infected mice at day 60. Similarly, aerosolization of TNFα and IFN-γ combined led to a very high degree of tuberculostatic activity in the lungs of infected animals, but not superior to that seen with either cytokine alone. Administration of similar amounts of cytokines by repeated intraperitoneal infusions led to a very marginal improvement in mouse resistance. These results suggest that localized cytokine administration may be beneficial in the treatment of lung diseases.

摘要

通过气溶胶途径给予白细胞介素-2(IL-2)、肿瘤坏死因子α(TNFα)和干扰素γ(IFN-γ)的免疫治疗潜力,在经空气传播途径感染结核分枝杆菌的小鼠身上进行了研究。用10⁴个结核分枝杆菌菌落形成单位(cfu)感染balb/c小鼠,在肺部微生物进行性生长后,感染后第35天所有小鼠死亡。如肺部结核分枝杆菌的生长情况所示,气溶胶化IL-2(每只小鼠100μg)并未促进对结核病抵抗力的增加。通过气溶胶途径给予IFN-γ或TNFα(100μg)导致肺部微生物生长显著减少,感染小鼠在第60天的存活率为100%。同样,TNFα和IFN-γ联合气溶胶化导致感染动物肺部具有非常高的抑菌活性,但并不优于单独使用任何一种细胞因子时的效果。通过重复腹腔内输注给予相似量的细胞因子,小鼠的抵抗力仅有非常微小 的改善。这些结果表明,局部给予细胞因子可能对肺部疾病的治疗有益。

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引用本文的文献

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: immune response, biomarkers, and therapeutic intervention.免疫反应、生物标志物与治疗干预。
MedComm (2020). 2024 Jan 6;5(1):e419. doi: 10.1002/mco2.419. eCollection 2024 Jan.

本文引用的文献

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Interleukin 2.白细胞介素2
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Adoptive protection of the Mycobacterium tuberculosis-infected lung. Dissociation between cells that passively transfer protective immunity and those that transfer delayed-type hypersensitivity to tuberculin.结核分枝杆菌感染肺部的过继性保护。被动转移保护性免疫的细胞与转移对结核菌素迟发型超敏反应的细胞之间的分离。
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[Importance of recent advances in our understanding of antimicrobial cell-mediated immunity to the International Union for the Prevention of Tuberculosis].[我们对抗微生物细胞介导免疫的最新认识进展对国际结核病防治联盟的重要性]
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Progress in the immunology of the mycobacterioses.分枝杆菌病免疫学研究进展
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Administration in vivo of recombinant interleukin 2 protects mice against septic death.体内注射重组白细胞介素-2可保护小鼠免于败血症死亡。
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Lung-specific delivery of cytokines induces sustained pulmonary and systemic immunomodulation in rats.细胞因子的肺特异性递送可在大鼠中诱导持续的肺部和全身免疫调节。
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The effect of gamma-interferon during Mycobacterium bovis (BCG) infection in athymic and euthymic mice.γ-干扰素在无胸腺小鼠和有胸腺小鼠感染牛分枝杆菌(卡介苗)期间的作用。
Microb Pathog. 1986 Apr;1(2):221-4. doi: 10.1016/0882-4010(86)90024-0.
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Endogenous tumor necrosis factor (cachectin) is essential to host resistance against Listeria monocytogenes infection.内源性肿瘤坏死因子(恶病质素)对于宿主抵抗单核细胞增多性李斯特菌感染至关重要。
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Interferon-gamma, the activated macrophage, and host defense against microbial challenge.干扰素-γ、活化巨噬细胞与宿主抵御微生物攻击
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