Chin A C, Morck D W, Merrill J K, Ceri H, Olson M E, Read R R, Dick P, Buret A G
Department of Biological Sciences, University of Calgary, Alta., Canada.
Am J Vet Res. 1998 Jun;59(6):765-71.
To determine whether tilmicosin alters neutrophil infiltration or function, induces neutrophil apoptosis, and affects accumulation of leukotriene B4 (LTB4) or tumor necrosis factor-alpha (TNF-alpha) in lungs of calves experimentally infected with Pasteurella haemolytica.
12 weight-ranked Holstein calves.
Calves were given 25% propylene glycol vehicle (n = 5) or tilmicosin (10 mg/kg of body weight; n = 6) subcutaneously, 18 hours and 15 minutes before intratracheal infection with 2 x 10(8) P haemolytica organisms. Two unmanipulated calves served as controls in some experiments. Rectal temperatures were recorded 15 minutes before, and at 3-hour intervals after infection for 24 hours. Samples obtained from bronchoalveolar lavage performed 3 and 24 hours after infection were used to assess colonization by P haemolytica, and neutrophil infiltration. Neutrophil phagocytosis of P haemolytica, membrane leakage as determined by trypan blue exclusion, oxidative function as determined by nitro blue tetrazolium reduction, and apoptosis, using electron microscopy and DNA fragmentation ELISA, were determined. SOluble TNF-alpha and LTB4 were measured from supernatants from bronchoalveolar lavage samples, using ELISA.
Treatment with tilmicosin resulted in significant (P < 0.05) clearance of P haemolytica and neutrophil apoptosis at 3 hours, and decreased concentration of LTB4 at 24 hours. Rectal temperatures, neutrophil infiltration, phagocytosis, oxidative functions, membrane leakage, and soluble TNF-alpha concentrations were not significantly affected by tilmicosin.
Tilmicosin effectively controlled P haemolytica infection, induced neutrophil apoptosis, reduced pulmonary inflammation, and did not affect neutrophil infiltration or function.
By inducing neutrophil apoptosis, tilmicosin prevents further amplification of inflammatory injury in P haemolytica-infected lungs.
确定替米考星是否会改变中性粒细胞浸润或功能、诱导中性粒细胞凋亡，以及影响实验性感染溶血巴斯德菌的犊牛肺中白三烯B4（LTB4）或肿瘤坏死因子-α（TNF-α）的蓄积。
12头按体重排序的荷斯坦犊牛。
在经气管内接种2×10⁸ 溶血巴斯德菌之前18小时15分钟，给犊牛皮下注射25%丙二醇载体（n = 5）或替米考星（10 mg/kg体重；n = 6）。在一些实验中，2头未进行处理的犊牛作为对照。在感染前15分钟以及感染后24小时内每隔3小时记录直肠温度。在感染后3小时和24小时进行支气管肺泡灌洗所获得的样本用于评估溶血巴斯德菌的定植情况以及中性粒细胞浸润情况。测定溶血巴斯德菌的中性粒细胞吞噬作用、通过台盼蓝排斥法测定的膜通透性、通过硝基蓝四氮唑还原法测定的氧化功能，以及使用电子显微镜和DNA片段化ELISA测定的凋亡情况。使用ELISA从支气管肺泡灌洗样本的上清液中测量可溶性TNF-α和LTB4。
替米考星治疗导致3小时时溶血巴斯德菌显著清除（P < 0.05）以及中性粒细胞凋亡，并使24小时时LTB4浓度降低。替米考星对直肠温度、中性粒细胞浸润、吞噬作用、氧化功能、膜通透性以及可溶性TNF-α浓度没有显著影响。
替米考星有效控制了溶血巴斯德菌感染，诱导了中性粒细胞凋亡，减轻了肺部炎症，并且未影响中性粒细胞浸润或功能。
通过诱导中性粒细胞凋亡，替米考星可防止溶血巴斯德菌感染的肺部炎症损伤进一步扩大。
