PROTECTION AGAINST A LETHAL DOSE OF ENDOTOXIN BY AN INHIBITOR OF TUMOR-NECROSIS-FACTOR PROCESSING
PROTECTION AGAINST A LETHAL DOSE OF ENDOTOXIN BY AN INHIBITOR OF TUMOR-NECROSIS-FACTOR PROCESSING
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DOI：
10.1038/370218a0
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发表时间：
1994-07-21
期刊：
影响因子：
64.8
通讯作者：
BLACK, RA
中科院分区：
文献类型：
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作者：
MOHLER, KM;SLEATH, PR;BLACK, RA
肿瘤坏死因子(肿瘤坏死因子-α/恶病质)在某些生理防御反应中起关键作用，但当产生过量时会对宿主机体造成严重损害。有两种形式的肿瘤坏死因子，一种是相对分子质量为26,000(26K)的II型膜蛋白，另一种是由细胞结合蛋白通过蛋白水解性裂解产生的可溶性17K形式(2，3)。这两种形式的肿瘤坏死因子和淋巴毒素-α(肿瘤坏死因子-β/淋巴毒素)是一种相关蛋白质，具有相似但明显不同的生物学活性(4-6)。抑制肿瘤坏死因子的释放，但不降低细胞相关活性或淋巴毒素-α水平的治疗剂，在防止肿瘤坏死因子诱导的损伤的同时，可能保留这些细胞因子的益处。在这里，我们描述了一种有效的肿瘤坏死因子处理抑制剂，并报告了它可以保护小鼠免受致死剂量的内毒素的伤害。
TUMOUR necrosis factor (tumour necrosis factor-alpha/cachectin) plays a critical role in certain physiological defensive responses but causes severe damage to the host organism when produced in excess(1). There are two forms of tumour necrosis factor, a type II membrane protein of relative molecular mass 26,000 (26K) and a soluble, 17K form generated from the cell-bound protein by proteolytic cleavage(2,3). The two forms of tumour necrosis factor and lymphotoxin-alpha (tumour necrosis factor-beta/lymphotoxin), a related protein, have similar but apparently not identical biological activities(4-6). A therapeutic agent which inhibited the release of tumour necrosis factor, but did not reduce the cell-associated activity or the level of lymphotoxin-alpha, might preserve the benefits of these cytokines while preventing tumour necrosis factor-induced damage. Here we describe a potent inhibitor of tumour necrosis factor processing and report that it protects mice from a lethal dose of endotoxin.