Barton M H, Bruce E H, Moore J N, Norton N, Anders B, Morris D D
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30628, USA.
Am J Vet Res. 1998 Jun;59(6):792-7.
To test efficacy of murine monoclonal, rabbit polyclonal recombinant equine or human tumor necrosis factor-alpha (rETNF or rHTNF, respectively) antibodies to inhibit native equine tumor necrosis factor (TNF) activity.
8 and 18 healthy adult horses for parts 1 and 2 of the study, respectively.
In part 1, supernates from endotoxin-activated peritoneal macrophages were incubated with various dilutions of each rETNF antibody and subsequently tested for TNF activity. Serum was also obtained from a horse 1 hour after infusion with 20 ng of endotoxin/kg of body weight and was incubated with various dilutions of rabbit polyclonal rHTNF antibody. In part 2, 20 ng of endotoxin/kg was infused in horses during a 30-minute period. Fifteen minutes after the endotoxin infusion was initiated, 1 of 3 preparations was infused: 0.1 mg of rabbit polyclonal (rHTNF antibody/kg, 0.1 mg of human IgG/kg, or 500 ml of 5% dextrose. Clinical and hematologic data were collected for 24 hours.
Compared with the monoclonal antibody, the rabbit polyclonal rETNF antibody was more effective in inhibiting TNF activity. The 50% effective doses of the murine monoclonal rETNF, rabbit polyclonal rETNF, and rabbit rHTNF antibodies were 1.8, 0.8, and 0.6 micrograms of antibody/ml, respectively. In part 2, endotoxin infusion resulted in significant alternations in all variables; however, differences among treatment groups were not significant.
Although murine monoclonal and rabbit polyclonal rETNF or rHTNF antibodies are capable of inhibiting native equine TNF activity in vitro, when given after initiation of endotoxemia, administration of 0.1 mg of rabbit polyclonal rHTNF/kg does not alter the response to infusion of endotoxin.
检测鼠单克隆抗体、兔多克隆重组马或人肿瘤坏死因子-α（分别为rETNF或rHTNF）抗体抑制天然马肿瘤坏死因子（TNF）活性的效果。
本研究第1部分和第2部分分别使用8匹和18匹健康成年马。
在第1部分中，将内毒素激活的腹腔巨噬细胞的上清液与每种rETNF抗体的不同稀释液孵育，随后检测TNF活性。还从一匹静脉注射20 ng内毒素/千克体重1小时后的马采集血清，并与兔多克隆rHTNF抗体的不同稀释液孵育。在第2部分中，在30分钟内向马静脉注射20 ng内毒素/千克体重。在内毒素注射开始15分钟后，注射3种制剂中的1种：0.1 mg兔多克隆（rHTNF抗体/千克体重）、0.1 mg人IgG/千克体重或500 ml 5%葡萄糖。收集24小时的临床和血液学数据。
与单克隆抗体相比，兔多克隆rETNF抗体在抑制TNF活性方面更有效。鼠单克隆rETNF、兔多克隆rETNF和兔rHTNF抗体的50%有效剂量分别为1.8、0.8和0.6微克抗体/毫升。在第2部分中，内毒素注射导致所有变量均出现显著变化；然而，各治疗组之间的差异不显著。
尽管鼠单克隆抗体和兔多克隆rETNF或rHTNF抗体在体外能够抑制天然马TNF活性，但在内毒素血症开始后给予0.1 mg兔多克隆rHTNF/千克体重，并不会改变对内毒素注射的反应。
