Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY 14853-6401.
Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY 14853-6401.
J Dairy Sci. 2018 Dec;101(12):11199-11217. doi: 10.3168/jds.2018-14869. Epub 2018 Oct 11.
The aim of this study was to evaluate the effects of treating Holstein cows with pegbovigrastim on periparturient diseases, milk production, and reproductive performance while exploring the mode of action of an immunomodulatory protein. Cows were randomly allocated to 1 of 2 treatments, untreated control (CTR, n = 423) and pegbovigrastim (PEG, n = 417). At 7 d from the anticipated calving date (d -7), cows allocated to PEG received a subcutaneous injection of 15 mg of pegylated recombinant bovine granulocyte colony stimulating factor (pegbovigrastim injection, Imrestor, Elanco Animal Health, Greenfield, IN). A second injection was administered within 24 h after calving (d 0). Blood samples were obtained from a subset of cows (CTR, n = 103; PEG, n = 102) at -7 and 0, 3, 7, and 14 d relative to parturition. Samples were used for hemogram and quantification of haptoglobin, nonesterified fatty acids, β-hydroxybutyrate, and trace and macro minerals. Vaginal cytobrush was performed on the same subset cows at d 0, 7, and 14 to assess the relative neutrophil count. Additionally, colostrum samples were collected to measure IgG, IgM, IgA, and lactoferrin concentrations. Postpartum disease occurrence was recorded from calving until 30 d in milk (DIM). Weekly milk yield was recorded for the first 12 wk after calving. Cows treated with PEG had a 3- to 4-fold increase in circulating polymorphonuclear leukocyte, lymphocyte, and monocyte numbers, with a peak at 3 d after treatment followed by a gradual decline, but the counts remained significantly greater compared with CTR at 14 DIM. The administration of PEG did not affect the incidence of clinical and subclinical mastitis, retained fetal membranes, metritis, puerperal metritis, and endometritis. Primiparous cows treated with PEG tended to have lower odds of developing hyperketonemia than CTR [odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.23 to 1.42]. Cows treated with PEG had higher odds of being diagnosed with lameness within 30 DIM compared with CTR (OR = 1.79, 95% CI = 1.16 to 2.76); however, we found no significant differences by 60 DIM. Treatment with PEG increased the odds of displaced abomasum (OR = 8.27, 95% CI = 1.02 to 66.6). Cows treated with PEG had higher odds of being diagnosed with 1 or more clinical diseases compared with CTR cows (OR = 1.39, 95% CI = 1.02 to 1.90). We observed no differences in linear scores or milk composition between treatments. Furthermore, primiparous cows treated with PEG produced more milk than CTR primiparous cows during the first 12 wk postpartum (PEG = 37.51 ± 0.66; CTR = 35.91 ± 0.65 kg), but no differences were observed on energy-corrected milk. Treatment did not alter reproductive performance; additionally, cows diagnosed with metritis or puerperal metritis and treated with PEG tended to have higher proportion of neutrophils in the vaginal mucosa when compared with CTR metritic cows. Although PEG treatment increased circulating polymorphonuclear leukocyte, monocyte, and lymphocyte numbers, as expected, it was detrimental to cow health because it increased morbidity.
本研究旨在评估对围产期疾病、牛奶产量和繁殖性能进行治疗的荷斯坦奶牛使用培格非司亭(pegbovigrastim)的效果,同时探索免疫调节蛋白的作用模式。奶牛被随机分配到 2 种治疗方法之一:未处理对照组(CTR,n=423)和培格非司亭(PEG,n=417)。在预期分娩日期前 7 天(d-7),接受 PEG 治疗的奶牛接受了 15mg 聚乙二醇化重组牛粒细胞集落刺激因子(培格非司亭注射液,Imrestor,礼蓝动保,格林菲尔德,印第安纳州)的皮下注射。分娩后 24 小时内给予第二次注射(d0)。从一组奶牛(CTR,n=103;PEG,n=102)中采集血液样本,在分娩前 0、3、7 和 14 天采集。样本用于血液计数和测定结合珠蛋白、非酯化脂肪酸、β-羟丁酸以及痕量和常量矿物质。在同一亚组奶牛中,在 d0、7 和 14 时进行阴道细胞刷检,以评估相对中性粒细胞计数。此外,收集初乳样本以测量 IgG、IgM、IgA 和乳铁蛋白浓度。从产犊到 30 天泌乳(DIM)期间记录产后疾病的发生情况。产后第一 12 周每周记录牛奶产量。与 CTR 相比,PEG 治疗的奶牛循环中多形核白细胞、淋巴细胞和单核细胞数量增加了 3 到 4 倍,在治疗后 3 天达到峰值,随后逐渐下降,但在 14 DIM 时仍显著高于 CTR。PEG 的给药不会影响临床和亚临床乳腺炎、胎衣不下、子宫炎、产褥期子宫炎和子宫内膜炎的发生率。与 CTR 相比,PEG 治疗的初产奶牛发生酮血症的可能性较低[比值比(OR)=0.57,95%置信区间(CI)=0.23 至 1.42]。与 CTR 相比,PEG 治疗的奶牛在 30 DIM 内被诊断为跛行的可能性更高(OR=1.79,95%CI=1.16 至 2.76);然而,在 60 DIM 时没有发现显著差异。PEG 治疗增加了瘤胃移位(OR=8.27,95%CI=1.02 至 66.6)的可能性。与 CTR 奶牛相比,PEG 治疗的奶牛更有可能被诊断出患有 1 种或多种临床疾病(OR=1.39,95%CI=1.02 至 1.90)。我们在治疗之间没有观察到线性评分或牛奶成分的差异。此外,PEG 治疗的初产奶牛在产后第一 12 周产奶量高于 CTR 初产奶牛(PEG=37.51±0.66;CTRL=35.91±0.65kg),但在能量校正乳中没有差异。治疗并没有改变繁殖性能;此外,与 CTR 子宫炎奶牛相比,患有子宫炎或产褥期子宫炎并接受 PEG 治疗的奶牛阴道黏膜中的中性粒细胞比例更高。尽管 PEG 治疗增加了循环中多形核白细胞、单核细胞和淋巴细胞的数量,但正如预期的那样,它对奶牛的健康是有害的,因为它增加了发病率。