Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Adv Exp Med Biol. 2009;666:64-77. doi: 10.1007/978-1-4419-1601-3_5.
The immune system functions by maintaining a delicate balance between the activities of pro-inflammatory and anti-inflammatory pathways. Unbalanced activation of these pathways often leads to the development of serious inflammatory diseases. TNF (Tumor Necrosis Factor) is a key pro-inflammatory cytokine, which can cause several inflammatory diseases when inappropriately up-regulated. Inhibition of TNF activities by using modulatory recombinant proteins has become a successful therapeutic approach to control TNF activity levels but these anti-TNF reagents also have risks and certain limitations. Biological molecules with a different mode of action in regulating TNF biology might provide a clinically useful alternative to the current therapeutics or in some cases might be efficacious in combination with existinganti-TNF therapies. TNF is also a powerful host defense cytokine commonly induced in the host response against various invading pathogens. Many viral pathogens can block TNF function by encoding modulators of TNF, its receptors or downstream signaling pathways. Here, we review the known virus-encoded TNF inhibitors and evaluate their potential as alternative future anti-TNF therapies.
免疫系统通过维持促炎和抗炎途径之间的微妙平衡来发挥作用。这些途径的不平衡激活常常导致严重炎症性疾病的发生。TNF（肿瘤坏死因子）是一种关键的促炎细胞因子，当其过度表达时会引发多种炎症性疾病。使用调节性重组蛋白抑制 TNF 的活性已成为控制 TNF 活性水平的成功治疗方法，但这些抗 TNF 试剂也存在风险和某些局限性。具有不同调节 TNF 生物学作用模式的生物分子可能为当前治疗方法提供一种临床有用的替代方法，或者在某些情况下与现有抗 TNF 疗法联合使用可能具有疗效。TNF 也是一种强大的宿主防御细胞因子，通常在宿主对各种入侵病原体的反应中诱导产生。许多病毒病原体可以通过编码 TNF、其受体或下游信号通路的调节剂来阻断 TNF 的功能。在这里，我们综述了已知的病毒编码的 TNF 抑制剂，并评估了它们作为替代未来抗 TNF 疗法的潜力。
