通过瘤坏死因子处理因子的抑制剂,防止致命剂量的内毒素的保护
K M Mohler1, P R Sleath, J N Fitzner
1Immunex Research and Development Corporation, Seattle, Washington 98101.
Nature
|July 21, 1994
概括
一种新型的抑制剂阻断瘤亡因子 (TNF) 释放,保持有益的免疫反应,同时防止过度TNF诱导的损伤. 这一发现可以保护小鼠免受致命的内毒素影响.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 瘤坏死因子 (TNF),也称为TNF-alpha或卡切丁,对于宿主防御至关重要,但在过度生产时会造成重大损害.
- TNF存在于26K型II膜蛋白和可溶性17K形式,来自蛋白质分解裂变.
- TNF和相关的淋巴毒素-α (TNF-β) 具有相似的生物活性.
研究的目的:
- 开发一种选择性抑制TNF释放的治疗剂.
- 为了保持有益的细胞因子功能,同时减轻TNF诱导的病理.
- 评估一种新型TNF处理抑制剂的保护作用.
主要方法:
- 描述一种向TNF处理的强效抑制剂.
- 给小鼠使用该抑制剂.
- 对接受治疗的小鼠暴露于致命剂量的内毒素.
主要成果:
- 开发的药物有效地抑制了瘤亡因子的处理.
- 用抑制剂治疗的小鼠证明了对致命的内毒素挑战的保护.
- 抑制剂的作用特异于TNF释放,不影响细胞相关活性或淋巴毒素α水平.
结论:
- 选择性抑制TNF释放是一种可行的治疗策略.
- 已识别的抑制剂在预防TNF介导损伤方面表现有前途.
- 这种方法可以保护宿主防御机制,同时防止有害的炎症反应.
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