肿瘤坏死因子：乙型肝炎病毒清除的关键

StephenW

Tumor necrosis factor: The key to hepatitis B viral clearance

    I-Tsu Chyuan & Ping-Ning Hsu

Cellular and Molecular Immunology | Download Citation

The immunopathogenesis of hepatitis B virus (HBV) involves a complex interaction of innate and adaptive immune response associated with several cytokines. However, due to experimental limitations, very limited and even no activation of the innate immune response can be demonstrated in acute HBV infection. The role of innate immunity and the key innate effectors for HBV clearance is still uncertain. It is also not clear whether clinical use of TNF inhibitors in treating rheumatoid arthritis and other autoimmune disease patients with chronic HBV infection would affect viral reactivation. However, in a recent paper in Cell Mol Immunol, Chyuan et al. reported that under TNF-α blockade, HBV viral clearance was impaired with persistent elevated HBV viral load in a dose and temporal-dependent manner.1 It demonstrates that a deficiency of TNF-α reduces viral clearance and promotes HBV persistence in a mouse model, and the impairment of HBV clearance under anti-TNF-α occurs at an early time point of HBV infection, suggesting that HBV may reactivate during therapy with TNF inhibitors. The results together with previous reports support that TNF is a key innate cytokine required to clear HBV.2, 3 It also provides evidence that therapy with TNF inhibitors may impair immune response to HBV clearance.

StephenW

肿瘤坏死因子：乙型肝炎病毒清除的关键

    I-Tsu Chyuan和Ping-Ning Hsu

细胞和分子免疫学|下载引文

乙型肝炎病毒（HBV）的免疫发病机制涉及与几种细胞因子相关的先天性和适应性免疫应答的复杂相互作用。然而，由于实验限制，在急性HBV感染中可以证明先天免疫应答的非常有限甚至没有活化。先天免疫的作用和HBV清除的关键先天效应物仍然不确定。尚不清楚TNF抑制剂在治疗类风湿性关节炎和其他慢性HBV感染的自身免疫性疾病患者中的临床应用是否会影响病毒再激活。然而，最近在Cell Mol Immunol，Chyuan等人的论文中。据报道，在TNF-α阻断下，HBV病毒清除率受到持续升高的HBV病毒载量的影响，呈剂量和时间依赖性.1它表明TNF-α缺乏会降低病毒清除率并促进小鼠模型中HBV的持续存在，并且抗-TNF-α下HBV清除的损害发生在HBV感染的早期时间点，表明在用TNF抑制剂治疗期间HBV可能再活化。结果与先前的报道一起支持TNF是清除HBV所需的关键先天细胞因子[2,3]。它还提供了TNF抑制剂治疗可能削弱对HBV清除免疫反应的证据。

StephenW

https://www.nature.com/articles/ ... Id=MTQ4Mjg2MDY3MwS2

"So far, with the lack of type I IFN response, the TNF pathway is the only innate response demonstrated to play a key role in HBV clearance. Nevertheless, it is necessary to clarify how innate immune cells are triggered and regulated to produce TNF-α during HBV infection. As one possible mechanism that we have previously reported, HBV core protein is sensed by the innate immune system to induce TNF-α production and thereby viral clearance; which can also be abolished by TNF-α blockade.2"
“到目前为止，由于缺乏I型IFN反应，TNF途径是唯一在HBV清除中发挥关键作用的先天反应。然而，有必要澄清先天免疫细胞如何被触发和调节以产生TNF- HBV感染期间的α。作为我们之前报道的一种可能的机制，HBV核心蛋白被先天免疫系统感知，诱导TNF-α的产生，从而导致病毒清除;也可以通过TNF-α阻断来消除。