This pilot study provides a preliminary assessment of the impact of genotype on acute innate immune pro-inflammatory, metabolic and endocrine responses to repeated lipopolysaccharide (LPS) administered to growing heifers. Heifers (n = 4/genotype) were from unselected (stable milk yield since 1964, UH) or contemporary (CH) Holstein cows that differed in milk yield (6200 vs 11,100 kg milk/305 d) or from contemporary Black Angus (CA) cows bred to contemporary Red Angus bulls. Heifers were challenged with iv administration of 0.5 μg LPS/kg body weight on day 1 (Challenge 1) and d 5 (Challenge 2) of study to assess endotoxin tolerance. Plasma was collected at -1, -0.5, 0, 1, 2, 3, 4, 6, 8, and 24 h relative to each LPS administration. Rectal body temperature (BT) was measured before each blood sampling and at 5 and 7 h. Data were analyzed by repeated measures with sampling time as the repeated effect. Each genotype had at least one pro-inflammatory response that indicated it might have a more robust response than the other genotypes. The CH heifers had a greater TNF-α response, UH heifers had greater IL-6 and XO responses and CA heifers had greater BT and SAA response to LPS than the other genotypes. There was a genotype by time by interaction as cortisol peaked earlier in CH and UH than in CA heifers. Glucose response was less in CA and insulin response was greater in CH heifers. Endotoxin tolerance to LPS was evident as pro-inflammatory, cortisol, glucose and insulin responses were less during Challenge 2 than during Challenge 1. Differences among genotypes during Challenge 1 were eliminated during Challenge 2 except for the greater SAA response in CA heifers and indicate the potential for differential impacts of genotype on the development of endotoxin tolerance. Specific reasons for these effects of genotype are not clear from these data but the results support the hypothesis for differential innate immune signaling among these bovine genotypes.

中文翻译：

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牛基因型对小母牛对重复脂多糖（LPS）施用的先天免疫应答的影响。

这项初步研究提供了基因型对对生长中的小母牛重复施用脂多糖（LPS）的急性先天免疫促炎，代谢和内分泌反应的影响的初步评估。小母牛（n = 4 /基因型）来自未选择的（自1964年以来，牛奶产量稳定，UH）或当代（CH）荷斯坦奶牛，其牛奶产量不同（6200对11,100 kg牛奶/ 305 d），或来自当代黑安格斯（CA）母牛繁殖给当代红安格斯公牛。在研究的第1天（挑战1）和第5天（挑战2）静脉注射0.5μgLPS / kg体重的母牛，以评估其对内毒素的耐受性。相对于每次LPS给药，分别在-1，-0.5、0、1、2、3、4、6、8和24小时收集血浆。在每次抽血前以及第5和第7小时测量直肠体温（BT）。通过重复测量以采样时间作为重复效应来分析数据。每个基因型至少有一个促炎反应，表明它可能比其他基因型有更强的反应。与其他基因型相比，CH小母牛的TNF-α应答更大，UH小母牛的IL-6和XO应答更大，CA小母牛对LPS的BT和SAA应答更大。通过交互作用，存在一种按时间分型的基因型，因为在CH和UH中皮质醇的峰值早于在CA母牛中。在CA中，葡萄糖反应较少，而在CH小母牛中，胰岛素反应较大。内毒素对LPS的耐受性很明显，因为在挑战2中促炎，皮质醇，葡萄糖和胰岛素反应比在挑战1中少。在挑战2中消除了挑战1中基因型之间的差异，除了CA小母牛对SAA的反应更大外，这表明基因型对内毒素耐受性发展产生不同影响的潜力。从这些数据尚不清楚引起这些基因型影响的具体原因，但结果支持了这些牛基因型之间先天免疫信号差异的假说。