Tumor necrosis factor activity in the circulation of horses given endotoxin.
Tumor necrosis factor activity in the circulation of horses given endotoxin.
复制标题
给予内毒素的马循环中的肿瘤坏死因子活性。
DOI：
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发表时间：
1991
影响因子：
1
通讯作者：
Skelley La
中科院分区：
文献类型：
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作者：
Robert J. MacKay;Merritt Am;Zertuche Jm;M. Whittington;Skelley La
对注射内毒素的马的血清和血浆进行细胞毒活性检测。L929和WEHI 164克隆13均对马血清的细胞毒作用敏感；然而，由于在WEHI测定中使用异丙醇引起的沉淀伪影限制了该测定的使用，使其仅限于含有少于2毫克/毫升蛋白质的样品。马驹注射5微克/千克的亚致死剂量脂多糖（LPS），成年马注射低剂量脂多糖（30微克/千克/小时，持续4小时），在脂多糖注射开始后30分钟至4小时内采集的所有血清或血浆样本中检测到细胞毒活性。在连续或大量注射LPS的马中，循环细胞毒活性在1至2小时达到峰值，然后急剧下降。LPS输注后的发热与循环细胞毒活性的出现一致，但即使在细胞毒活性消失后，温度仍然很高。1 mg/kg氟尼辛大聚氨胺能减弱低剂量LPS连续输注对马的解热作用，但对循环细胞毒活性无显著影响。将血清样本与针对部分人肿瘤坏死因子（TNF）的抗体孵育，可去除90%以上的血清细胞毒性，这强烈表明细胞毒性活性可归因于TNF。这些发现与TNF是马内毒素作用的早期介质的假设是一致的。
Serum and plasma from horses injected with endotoxin was examined for cytotoxic activity. Each of the cell lines, L929 and WEHI 164 clone 13, was sensitive to the cytotoxic effects of equine serum; however, a precipitation artifact caused by the use of isopropanol in the WEHI assay limited the use of this assay to samples containing less than 2 mg of protein/ml. In foals treated with a sublethal IV bolus of 5 micrograms of lipopolysaccharide (LPS)/kg and in adult horses given a low-dose continuous infusion of LPS (30 ng/kg/h for 4 hours), cytotoxic activity was detected in all serum or plasma samples taken between 30 minutes and 4 hours after LPS infusion began. In horses given either continuous or bolus LPS infusions, circulating cytotoxic activity peaked at 1 to 2 hours before decreasing sharply. The onset of pyrexia after LPS infusion coincided with the appearance of circulating cytotoxic activity, but the temperature remained high, even after cytotoxic activity disappeared. Treatment of horses with flunixin meglumine (1 mg/kg) appeared to blunt the pyrexic effect of low-dose continuous LPS infusion, but had no significant effect on circulating cytotoxic activity. Incubation of serum samples with an antibody raised against a portion of human tumor necrosis factor (TNF) resulted in the removal of greater than 90% of serum cytotoxicity, suggesting strongly that the cytotoxic activity was attributable to TNF. These findings are consistent with the hypothesis that TNF is an early acting mediator of the effects of endotoxin in the horse.