Acute in vivo effects of human recombinant tumor necrosis factor.
Acute in vivo effects of human recombinant tumor necrosis factor.
复制标题
DOI：
--
复制
发表时间：
1987-06
期刊：
影响因子：
--
通讯作者：
Daniel G. Remick;Robin G. Kunkel;Larrick Jw;S. L. Kunkel
中科院分区：
文献类型：
--
作者：
Daniel G. Remick;Robin G. Kunkel;Larrick Jw;S. L. Kunkel
肿瘤坏死因子是一种肽类细胞因子，可诱导某些肿瘤的出血性坏死，并导致晚期感染性疾病中观察到的严重恶病质。我们评价了小鼠静脉注射纯化的重组人肿瘤坏死因子的急性效应。通过流式细胞术分析确定，在低至0.01微克/小鼠（0.00045 mg/kg）的剂量下，发生外周血淋巴细胞减少症和嗜中性粒细胞增多症。在1 μ g/小鼠时，淋巴细胞减少是相对的（21 +/- 3% vs 65 +/- 3%; p <0.001，处理组vs对照组）和绝对的（62 +/- 10 vs 229 +/- 29 X 10（4）个细胞/ml，p <0.001）。嗜中性粒细胞也是相对的（79 +/- 3% vs 34 +/- 3%; p <0.001，处理组vs对照组）和绝对的（237 +/- 26 vs 110 +/- 13 X 10（4）细胞/ml; p <0.001）。嗜中性粒细胞增多是由于成熟和未成熟细胞的增加。在较高剂量下，动物发生低血容量性休克，红细胞压积增加，并发生水样腹泻。小肠显微镜检查显示绒毛坏死。小肠的超微结构研究证实了坏死，还显示了严重的内皮细胞损伤、核固缩、潘氏细胞颗粒的胞吐作用以及红细胞和中性粒细胞外渗到小肠中。发生血管渗漏综合征，液体优先流失到小肠和大肠中。这些数据证明了纯化的人重组肿瘤坏死因子在体内的有效作用。
Tumor necrosis factor is a peptide cytokine that induces hemorrhagic necrosis of some tumors and is responsible for the severe cachexia observed in advanced infectious diseases. We evaluated the acute effects of intravenous administration of purified human recombinant tumor necrosis factor in mice. With as little as 0.01 microgram/mouse (0.00045 mg/kg) a peripheral blood lymphopenia and neutrophilia developed as determined by flow cytometric analysis. At 1 microgram/mouse, the lymphopenia was both relative (21 +/- 3% versus 65 +/- 3%; p less than 0.001 treated versus control) and absolute (62 +/- 10 versus 229 +/- 29 X 10(4) cells/ml p less than 0.001). The neutrophilia was also relative (79 +/- 3% versus 34 +/- 3%; p less than 0.001 treated versus control) and absolute (237 +/- 26 versus 110 +/- 13 X 10(4) cell/ml; p less than 0.001). The neutrophilia was due to an increase in both mature and immature cells. At the higher doses the animals developed hypovolemic shock with an increased hematocrit and watery diarrhea occurred. Microscopic examination of the small bowel disclosed necrosis of the villi. Ultrastructural studies of the small bowel confirmed the necrosis and also showed severe endothelial cell damage, pyknotic nuclei, exocytosis of Paneth cell granules, and extravasation of red blood cells and neutrophils into the interstitium. A vascular leak syndrome developed with preferential fluid loss into the small and large bowel. These data demonstrate the potent in vivo effects of purified human recombinant tumor necrosis factor.