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Colchicine prevents tumor necrosis factor-induced toxicity in vivo.

机译:秋水仙碱可预防体内肿瘤坏死因子诱导的毒性。

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Tumor necrosis factor (TNF) toxicity was induced in vivo by intravenous administration of 15 micrograms of recombinant murine TNF-alpha per kg to galactosamine-sensitized mice. Within 8 h, the animals developed a fulminant hepatitis. Intravenous administration of 0.5 mg of colchicine per kg at 19 and 4 h prior to TNF challenge protected the animals against hepatitis. Lipopolysaccharide (LPS)-stimulated, bone marrow-derived macrophages from C3H/HeN mice released significant amounts of TNF in vitro. When such macrophages were intravenously given to LPS-resistant galactosamine-sensitized C3H/HeJ mice, these animals died within 24 h. Preincubation of these transferred macrophages with colchicine did not suppress the LPS-inducible TNF release from these cells. Concordantly, administration of macrophages exposed to colchicine in vitro resulted in full lethality. However, in vivo pretreatment of C3H/HeJ mice with colchicine 19 and 4 h prior to the transfer of LPS-stimulated macrophages prevented lethality. In LPS-responsive NMRI mice which had been protected against galactosamine-LPS-induced hepatitis by pretreatment with colchicine, TNF was still released into the blood. We conclude from our findings that the in vivo protection by colchicine is mediated by blocking TNF action on target cells while the effector cells of LPS toxicity, i.e., the macrophages, remain responsive.
机译:通过向半乳糖胺致敏的小鼠静脉内每公斤静脉注射15微克重组鼠TNF-α,可诱导体内肿瘤坏死因子(TNF)毒性。在8小时内,这些动物患上了暴发性肝炎。在TNF攻击前19和4小时,静脉内每公斤0.5 mg秋水仙碱给药可保护动物免于肝炎。来自C3H / HeN小鼠的脂多糖(LPS)刺激的骨髓巨噬细胞在体外释放了大量的TNF。当将这种巨噬细胞静脉内给予耐LPS的半乳糖胺敏化的C3H / HeJ小鼠时,这些动物在24小时内死亡。这些转移的巨噬细胞与秋水仙碱的预孵育不能抑制LPS诱导的TNF从这些细胞中释放。相应地,体外暴露于秋水仙碱的巨噬细胞的施用导致完全的致死性。但是,在转移LPS刺激的巨噬细胞之前的19和4 h,用秋水仙碱对C3H / HeJ小鼠进行体内预处理可防止致死性。在通过秋水仙碱预处理而被保护免受半乳糖胺-LPS诱导的肝炎的LPS反应性NMRI小鼠中,TNF仍释放到血液中。从我们的发现中我们得出结论,秋水仙碱的体内保护作用是通过阻断TNF对靶细胞的作用来介导的,而LPS毒性的效应细胞(即巨噬细胞)仍然具有响应性。

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