Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
J Dairy Sci. 2013 Jul;96(7):4406-18. doi: 10.3168/jds.2012-6455. Epub 2013 May 16.
Mastitis in dairy cows is typically treated with intramammary antibiotics. The combination of antibiotics with corticosteroids tends to have a large market share where these products are registered. Our objective was to investigate the effect of prednisolone in combination with cefapirin on the inflammatory response of experimentally induced Escherichia coli mastitis. Six midlactating Holstein-Friesian cows were challenged in 3 quarters with E. coli and treated at 4, 12, 24, and 36 h postinfection with 300 mg of cefapirin in 1 quarter and a combination of 300 mg of cefapirin and 20mg of prednisolone in another quarter. At 24h (n=3) or 48 h (n=3) postinfection cows were euthanized for tissue sampling. Clinical scores, somatic cell count, and California mastitis test scores, as well as IL-1β, IFN-γ, IL-4, and IL-10 levels and bacterial growth in milk, were measured every 6h. Experimental inoculation caused a moderate clinical mastitis in all cows in challenged, untreated quarters. The E. coli challenge strain was recovered from all infected quarters and confirmed by PCR-based fingerprinting. Challenged, untreated control quarters showed increased concentrations of all measured cytokines together with recruitment of polymorphonuclear neutrophilic leukocytes at 24 and 48 h postchallenge. Both treatments reduced udder swelling and sensitivity with no statistically significant difference between treatment groups. Administration of cefapirin alone or in combination with prednisolone resulted in significantly lower concentrations of IFN-γ, IL-1β, and IL-10 compared with challenged, untreated quarters. Treated quarters did show IL-4 production, but concentrations were significantly decreased compared with untreated, challenged quarters. Quarters treated with the combination of cefapirin and prednisolone showed a significantly lower concentration of IL-4 compared with cefapirin-only treatment. At both 24 and 48 h postinoculation, the level of polymorphonuclear neutrophilic leukocyte recruitment was lowest in challenged quarters treated with a combination of cefapirin and prednisolone, followed by cefapirin alone. Taken together, treatment with cefapirin alone inhibited bacterial growth in milk and reduced the host inflammatory responses. Addition of prednisolone to cefapirin had a synergistic effect, resulting in a lower density of leukocytes in tissue and milk and a quicker restoration of milk quality.
奶牛乳腺炎通常采用乳房内抗生素治疗。抗生素与皮质类固醇的联合应用在这些产品注册的地方往往占有很大的市场份额。我们的目的是研究在实验性诱导的大肠杆菌乳腺炎中，泼尼松龙与头孢匹林联合应用对炎症反应的影响。将 6 头泌乳中期荷斯坦-弗里森奶牛的 3 个乳区用大肠杆菌攻毒，在感染后 4、12、24 和 36 小时，每个乳区用 300mg 头孢匹林，另一个乳区用 300mg 头孢匹林和 20mg 泼尼松龙联合治疗。在感染后 24 小时（n=3）或 48 小时（n=3）处死奶牛进行组织取样。每 6 小时测量临床评分、体细胞计数和加利福尼亚乳房炎测试评分，以及白细胞介素-1β、干扰素-γ、白细胞介素-4 和白细胞介素-10 水平以及牛奶中的细菌生长情况。所有攻毒的未处理乳区的奶牛均发生中度临床乳腺炎。从所有感染的乳区中回收大肠杆菌攻毒株，并通过基于 PCR 的指纹图谱进行确认。未处理的对照乳区在攻毒后 24 和 48 小时，所有测量的细胞因子浓度增加，并招募多形核中性粒细胞。单独使用头孢匹林或与泼尼松龙联合使用均可减轻乳房肿胀和敏感性，但两组之间无统计学差异。与未处理的攻毒乳区相比，单独使用头孢匹林或与泼尼松龙联合使用可显著降低 IFN-γ、IL-1β 和 IL-10 的浓度。用头孢匹林和泼尼松龙治疗的乳区确实产生了 IL-4，但与未处理的攻毒乳区相比，浓度显著降低。与单独使用头孢匹林相比，头孢匹林和泼尼松龙联合治疗的乳区的 IL-4 浓度显著降低。在攻毒后 24 和 48 小时，用头孢匹林和泼尼松龙联合治疗的攻毒乳区多形核中性粒细胞的募集水平最低，其次是单独使用头孢匹林。综上所述，单独使用头孢匹林可抑制牛奶中的细菌生长，降低宿主炎症反应。头孢匹林中加入泼尼松龙具有协同作用，可降低组织和牛奶中的白细胞密度，并更快地恢复牛奶质量。
