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聚乙二醇化重组人粒细胞集落刺激因子预防美国商业奶牛场初产和经产围产期奶牛自然发生临床型乳腺炎的疗效及临床安全性

Efficacy and clinical safety of pegbovigrastim for preventing naturally occurring clinical mastitis in periparturient primiparous and multiparous cows on US commercial dairies.

作者信息

Canning Peter, Hassfurther Renee, TerHune Terry, Rogers Karen, Abbott Scott, Kolb David

机构信息

Bioproduct Innovation, ELANCO Animal Health, Greenfield, IN 46062.

Bioproduct Innovation, ELANCO Animal Health, Greenfield, IN 46062.

出版信息

J Dairy Sci. 2017 Aug;100(8):6504-6515. doi: 10.3168/jds.2017-12583. Epub 2017 Jun 7.

DOI:10.3168/jds.2017-12583
PMID:28601453
Abstract

Periparturient dairy cows experience impaired immune function, exhibited as a transient decrease in neutrophil function. This decrease in immune competence is associated with an increase in susceptibility to bacterial infections, including mastitis and metritis. Bovine granulocyte colony stimulating factor (bG-CSF) is an endogenous protein that enhances neutrophil bactericidal functions and increases the production of neutrophils from bone marrow precursors. Administration of pegbovigrastim (recombinant bG-CSF covalently bound to polyethylene glycol) around the time of calving has been shown to reduce the incidence of new clinical mastitis cases in a natural disease model system. To further explore the application of pegbovigrastim under herd management systems typical of those found in the US dairy industry, we conducted a multicenter field study to evaluate the efficacy and clinical safety of pegbovigrastim administered to multiparous cows and heifers approximately 7 d before calving and within 24 h of calving. Responses of treated cows were compared with those of animals treated with sterile saline. Animals treated with pegbovigrastim exhibited 4- to 5-fold increases in circulating neutrophil numbers within 24 h of treatment initiation, and this increase persisted at least a week beyond the second dose. Pegbovigrastim-treated animals exhibited a 35% decrease in the incidence of clinical mastitis relative to the controls during the first 30 d of lactation. Animals treated with pegbovigrastim also exhibited a 52% reduction in failure to return to visual estrus within 80 d of calving. We observed no differences in somatic cell count or milk composition between treated and control animals. We also found no differences in the duration of pregnancy or proportion of viable calves in treated cows relative to control animals. These results indicate that administration of pegbovigrastim provides a well-tolerated, novel approach to overcoming periparturient immune suppression, resulting in reduced susceptibility to clinical mastitis during early lactation.

摘要

围产期奶牛的免疫功能受损,表现为中性粒细胞功能短暂下降。免疫能力的这种下降与包括乳腺炎和子宫炎在内的细菌感染易感性增加有关。牛粒细胞集落刺激因子(bG-CSF)是一种内源性蛋白质,可增强中性粒细胞的杀菌功能,并增加骨髓前体细胞产生的中性粒细胞数量。在产犊前后给予培戈维司亭(与聚乙二醇共价结合的重组bG-CSF)已被证明可降低自然疾病模型系统中新发临床乳腺炎病例的发生率。为了进一步探索培戈维司亭在美国奶牛行业典型的畜群管理系统中的应用,我们进行了一项多中心现场研究,以评估在产犊前约7天和产犊后24小时内给多胎奶牛和小母牛施用培戈维司亭的疗效和临床安全性。将治疗奶牛的反应与用无菌生理盐水治疗的动物的反应进行比较。用培戈维司亭治疗的动物在开始治疗后24小时内循环中性粒细胞数量增加了4至5倍,并且这种增加在第二次给药后至少持续了一周。与对照组相比,在泌乳的前30天内,用培戈维司亭治疗的动物临床乳腺炎的发生率降低了35%。用培戈维司亭治疗的动物在产犊后80天内未恢复明显发情的比例也降低了52%。我们观察到治疗组和对照组动物的体细胞计数或牛奶成分没有差异。我们还发现,与对照动物相比,治疗奶牛的怀孕持续时间或存活犊牛比例没有差异。这些结果表明,施用培戈维司亭提供了一种耐受性良好的新方法来克服围产期免疫抑制,从而降低早期泌乳期间临床乳腺炎的易感性。

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