Tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired IFN-gamma production by spleen cells from human visceral leishmaniasis patients

Singh Neetu; Kumar Rajiv; Engwerda Christian; Sacks David; Nylen Susanne; Sundar Shyam

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Tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired IFN-gamma production by spleen cells from human visceral leishmaniasis patients

机译：肿瘤坏死因子α中和对寄生虫负担没有直接影响，但会导致人内脏利什曼病患者脾细胞的IFN-γ产生受损

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The pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha has an important role in control of experimental Leishmania donovani infection. Less is known about the role of TNF-alpha in human visceral leishmaniasis (VL). Evidence for a protective role is primarily based on case reports of VL development in individuals treated with TNF-alpha neutralizing antibody. In this study, we have evaluated how TNF-alpha neutralization affects parasite replication and cytokine production in ex vivo splenic aspirates (SA) from active VL patients. The effect of TNF-alpha neutralization on cell mediated antigen specific responses were also evaluated using whole blood cultures. Neutralization of TNF-alpha did not affect parasite numbers in SA cultures. Interferon (IFN)-gamma levels were significantly reduced, but interleukin (IL)-10 levels were unchanged in these cultures. Leishmania antigen stimulated SA produced significant TNF-alpha which suggests that TNF-alpha is actively produced in VL spleen. Further it stimulates IFN-gamma production, but no direct effect on parasite replication. (C) 2016 Elsevier Ltd. All rights reserved.

机译：促炎性细胞因子肿瘤坏死因子（TNF）-α在控制实验性利什曼原虫多诺万尼感染中具有重要作用。 TNF-α在人类内脏利什曼病（VL）中的作用鲜为人知。保护作用的证据主要基于用TNF-α中和抗体治疗的个体中VL发育的病例报告。在这项研究中，我们评估了TNF-α的中和作用如何影响活动性VL患者离体脾脏抽吸物（SA）中的寄生虫复制和细胞因子产生。还使用全血培养物评估了TNF-α中和作用对细胞介导的抗原特异性反应的影响。 TNF-α的中和作用不影响SA培养物中的寄生虫数量。在这些培养物中，干扰素（IFN）-γ水平显着降低，但白介素（IL）-10水平未发生变化。利什曼原虫抗原刺激的SA产生显着的TNF-α，这表明TNF-α在VL脾脏中活跃产生。此外，它刺激IFN-γ的产生，但对寄生虫复制没有直接影响。（C）2016 Elsevier Ltd.保留所有权利。

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《Cytokine》 |2016年第null期|共7页
作者
Singh Neetu; Kumar Rajiv; Engwerda Christian; Sacks David; Nylen Susanne; Sundar Shyam;
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正文语种 eng
中图分类细胞生物学;
关键词
Visceral leishmaniasis; TNF-alpha; Enbrel; IL-10; Splenic aspirate; Whole blood assay;

机译：内脏利什曼病;TNF-α;Enbrel;IL-10;脾脏吸出物;全血测定;

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1. Tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired IFN-gamma production by spleen cells from human visceral leishmaniasis patients [J] . Singh Neetu, Kumar Rajiv, Engwerda Christian, Cytokine . 2016,第Null期

机译：肿瘤坏死因子α中和对寄生虫负担没有直接影响，但会导致人内脏利什曼病患者脾细胞的IFN-γ产生受损
2. Ligand of scavenger receptor class A indirectly induces maturation of human blood dendritic cells via production of tumor necrosis factor-alpha. [J] . Jin JO, Park HY, Xu Q, Blood: The Journal of the American Society of Hematology . 2009,第23期

机译：清道夫受体A类的配体通过产生肿瘤坏死因子-α间接诱导人血树突状细胞成熟。
3. Captopril inhibits the production of tumor necrosis factor-alpha by human mononuclear cells in patients with congestive heart failure. [J] . Zhao SP, Xie XM Clinica chimica acta: International journal of clinical chemistry and applied molecular biology . 2001,第1a2期

机译：卡托普利抑制充血性心力衰竭患者的人单核细胞产生肿瘤坏死因子-α。
4. Tumor Necrosis Factor-alpha (TNF-alpha) Gene -238 Single Nucleotide Polymorphism (SNP) Is Associated with Low TNF-a Production from Peripheral Blood Mononuclear Cells (PBMCs) in Japanese [C] . K. Shuno, M. Aoyama, S. Fudo, Conference on Shock . 2008

机译：肿瘤坏死因子-α（TNF-α）基因-238单核苷酸多态性（SNP）与日本外周血单核细胞（PBMC）的低TNF-A生产相关
5. Intracellular Signal Transduction Mechanisms Regulating the Activation of Human Bronchial Epithelial Cells by Interleukin-17A, Interleukin-27, Tumor Necrosis Factor-alpha and Human Basophils in Inflammatory Diseases [D] . Cao, Ju 2010

机译：调节人白细胞介素17A，白细胞介素27，肿瘤坏死因子-α和人类嗜碱性粒细胞在炎性疾病中激活人支气管上皮细胞的细胞内信号转导机制
6. Tumor Necrosis Factor Alpha neutralization has no direct effect on parasite burden but causes impaired IFN-γ production by spleen cells from human visceral leishmaniasis patients [O] . Neetu Singh, Rajiv Kumar, Christian Engwerda, -1

机译：肿瘤坏死因子α中和对寄生虫负担没有直接影响但会导致人内脏利什曼病患者脾细胞的IFN-γ产生受损
7. Constitutive production of interleukin-6 and tumor necrosis factor- alpha from spontaneously proliferating T cells in patients with human T- cell lymphotropic virus type-I/II [O] . RB Lal, DL Rudolph 1991

机译：中白细胞介素-6和肿瘤坏死因子 - 从人T-细胞淋巴细胞型病毒型 - I / II患者中产生的白细胞介素-6和肿瘤坏死因子 - α
8. IL-1 and Tumor Necrosis Factor-Alpha Each Up-Regulate Both the Expression of IFN-Gamma Receptors and Enhance IFN-Gamma-Induced HLA-DR Expression on Human Monocytes and a Human Monocytic Cell Line (THP-1) [R] . Krakauer, T., Oppenheim, J. J. 1993

机译：IL-1和肿瘤坏死因子-α各自上调IFN-γ受体的表达并增强人单核细胞和人单核细胞系（THp-1）上IFN-γ诱导的HLa-DR表达

Tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired IFN-gamma production by spleen cells from human visceral leishmaniasis patients

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