• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Dynamic Changes in Pro- and Anti-Inflammatory Cytokine Profiles and Gamma Interferon Receptor Signaling Integrity Correlate with Tuberculosis Disease Activity and Response to Curative Treatment
【24h】

Dynamic Changes in Pro- and Anti-Inflammatory Cytokine Profiles and Gamma Interferon Receptor Signaling Integrity Correlate with Tuberculosis Disease Activity and Response to Curative Treatment

机译：促炎性和抗炎性细胞因子谱的动态变化以及γ干扰素受体信号完整性与结核病活动和对治疗的反应相关

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Pro- and anti-inflammatory cytokines and their signaling pathways play key roles in protection from and pathogenesis of mycobacterial infection, and their balance and dynamic changes may control or predict clinical outcome. Peripheral blood cells' capacity to produce proinflammatory (tumor necrosis factor alpha [TNF-α], interleukin-12/23p40 [IL-12/23p40], and gamma interferon [IFN-γ]) and anti-inflammatory (IL-10) cytokines in response to Mycobacterium tuberculosis or unrelated stimuli (lipopolysaccharide, phytohemagglutinin) was studied in 93 pulmonary tuberculosis (TB) patients and 127 healthy controls from Indonesia. Their cells' ability to respond to IFN-γ was examined to investigate whether M. tuberculosis infection can also inhibit IFN-γ receptor (IFN-γR) signaling. Although there was interindividual variability in the observed responses, the overall results revealed that M. tuberculosis-induced TNF-α and IFN-γ levels showed opposite trends. Whereas TNF-α production was higher in active-TB patients than in controls, IFN-γ production was strongly depressed during active TB, correlated inversely with TB disease severity, and increased during therapy. By contrast, mitogen-induced IFN-γ production, although lower in patients than in controls, did not change during treatment, suggesting an M. tuberculosis-specific and reversible component in the depression of IFN-γ. Depressed IFN-γ production was not due to decreased IL-12/IL-23 production. Importantly, IFN-γ-inducible responses were also significantly depressed during active TB and normalized during treatment, revealing disease activity-related and reversible impairment in IFN-γR signaling in TB. Finally, IFN-γ/IL-10 ratios significantly correlated with TB cure. Taken together, these results show that M. tuberculosis-specific stimulation of IFN-γ (but not TNF-α) production and IFN-γR signaling are significantly depressed in active TB, correlate with TB disease severity and activity, and normalize during microbiological TB cure. The depression of both IFN-γ production and IFN-γR signaling may synergize in contributing to defective host control in active TB.
机译：促炎和抗炎细胞因子及其信号通路在分枝杆菌感染的预防和发病机理中起着关键作用，它们的平衡和动态变化可能控制或预测临床结果。外周血细胞产生促炎（肿瘤坏死因子α[TNF-α]，白介素-12 / 23p40 [IL-12 / 23p40]和γ干扰素[IFN-γ]）和抗炎（IL-10）的能力在印度尼西亚的93名肺结核（TB）患者和127名健康对照中，研究了对结核分枝杆菌或无关刺激物（脂多​​糖，植物血凝素）应答的细胞因子。检查它们的细胞对IFN-γ反应的能力以研究是否 M。结核感染也可以抑制IFN-γ受体（IFN-γR）的信号传导。尽管观察到的反应存在个体差异，但总体结果显示， M。结核病诱导的TNF-α和IFN-γ水平呈相反趋势。尽管活动性结核病患者的TNF-α产生高于对照组，但活动性结核病期间的IFN-γ产生被强烈抑制，与结核病严重程度成反比，并在治疗期间增加。相比之下，尽管有丝分裂原诱导的IFN-γ产生虽然在患者中低于对照组，但在治疗过程中并没有改变，表明为 M。结核病的特异性和可逆性成分可降低IFN-γ。降低的IFN-γ产生不是由于IL-12 / IL-23产生的减少。重要的是，在活动性结核病期间，IFN-γ诱导的应答也显着降低，在治疗过程中也正常化，从而揭示了结核病中IFN-γR信号传导的疾病活动相关和可逆性损伤。最后，IFN-γ/ IL-10比率与结核病治愈显着相关。综合来看，这些结果表明 M。在活动性结核病中，结核特异性刺激IFN-γ（而不是TNF-α）的产生和IFN-γR信号显着降低，与结核病的严重程度和活性相关，并在微生物结核病治愈期间恢复正常。 IFN-γ产生和IFN-γR信号转导的降低可能协同作用，导致活性TB的宿主控制缺陷。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号