Rapid and sensitive assay of tumor necrosis factor-alpha gene transcription.
Rapid and sensitive assay of tumor necrosis factor-alpha gene transcription.
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快速、灵敏地检测肿瘤坏死因子-α 基因转录。
DOI：
10.1023/a:1011031719961
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发表时间：
2001
影响因子：
3.7
通讯作者：
Rojanasakul,Y
中科院分区：
文献类型：
--
作者：
Zhang,X;Ye,J;Wang,L;Manosroi,J;Shi,X;Rojanasakul,Y
肿瘤坏死因子-α是一种在感染和创伤后迅速出现的细胞因子(1，2)。它是一种免疫刺激剂，也是宿主抵抗感染性病原体和恶性肿瘤的重要介体(2，3)。然而，当调节异常时，即由于自身免疫反应或组织损伤，肿瘤坏死因子-α可引起严重的全身毒性，甚至死亡。高水平的肿瘤坏死因子-α与多种病理状态有关，如恶病质和脓毒症，过度表达肿瘤坏死因子-α的转基因动物会发展成病理炎症状态，包括多发性关节炎和中枢神经系统脱髓鞘[4，5]。此外，中和肿瘤坏死因子-α活性导致炎症性疾病模型以及关节炎和败血症患者的改善(4，6)。由于肿瘤坏死因子-α具有重要的生理和病理意义，已有几种肿瘤坏死因子-α调节药物被开发出来用于治疗。到目前为止，主要的治疗策略一直集中在肿瘤坏死因子-α抗体和拮抗剂上。抗体有几个优点，如靶向特异性超过其他治疗药物；然而，由于其潜在的免疫毒性，它们的使用在很大程度上受到了限制。虽然人们已经努力使抗体人源化以避免其免疫原性，但一些替代策略，包括使用小的非免疫原性分子的策略，越来越多地被作为抗体的替代品进行研究。
Tumor necrosis factor-alpha (TNF-α) is a cytokine that appears rapidly in response to infection and trauma (1, 2). It plays a beneficial role as an immunostimulant and important mediator of host defense against infectious agents and malignant tumors (2, 3). However, when abnormally regulated, ie, because of an autoimmune response or tissue injury, TNF-α can cause severe systemic toxicity and even death. High levels of TNF-α have been associated with various pathological states, such as cachexia and sepsis, and transgenic animals overexpressing TNF-α develop pathological inflammatory conditions, including polyarthritis and central nervous system demyelination (4, 5). Moreover, neutralization of TNF-α activity leads to improvement in models of inflammatory diseases and in patients with arthritis and sepsis (4, 6). Because of the physiologic and pathologic importance of TNF-α, several TNF-α-modulating drugs have been developed for therapeutic purposes. Major therapeutic strategies developed thus far have been focused on TNF-α antibodies and antagonists. Antibodies have several advantages, such as target specificity over other therapeutic agents; however, their use has been largely limited resulting from their potential immunotoxicity. Although great efforts have been made to humanize the antibodies to avoid their immunogenicity, several alternative strategies, including those using small non-immunogenic molecules, increasingly have been investigated as antibody replacements.