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慢性、非致病性母体免疫激活对子代产后肌肉和免疫结局的影响。

The effect of chronic, non-pathogenic maternal immune activation on offspring postnatal muscle and immune outcomes.

机构信息

Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA.

出版信息

J Anim Sci. 2024 Jan 3;102. doi: 10.1093/jas/skad424.

Abstract

The objective was to determine the effects of maternal inflammation on offspring muscle development and postnatal innate immune response. Sixteen first-parity gilts were randomly allotted to repeated intravenous injections with lipopolysaccharide (LPS; n = 8, treatment code INFLAM) or comparable volume of phosphate buffered saline (CON, n = 8). Injections took place every other day from gestational day (GD) 70 to GD 84 with an initial dose of 10 μg LPS/kg body weight (BW) increasing by 12% each time to prevent endotoxin tolerance. On GD 70, 76, and 84, blood was collected at 0 and 4 h postinjection via jugular or ear venipuncture to determine tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β concentrations. After farrowing, litter mortality was recorded, and the pig closest to litter BW average was used for dissection and muscle fiber characterization. On weaning (postnatal day [PND] 21), pigs were weighed individually and 2 barrows closest to litter BW average were selected for another study. The third barrow closest to litter BW average was selected for the postnatal LPS challenge. On PND 52, pigs were given 5 μg LPS/kg BW via intraperitoneal injection, and blood was collected at 0, 4, and 8 h postinjection to determine TNF-α concentration. INFLAM gilt TNF-α concentration increased (P < 0.01) 4 h postinjection compared to 0 h postinjection, while CON gilt TNF-α concentration did not differ between time points. INFLAM gilt IL-6 and IL-1β concentrations increased (P = 0.03) 4 h postinjection compared to 0 h postinjection on GD 70, but did not differ between time points on GD 76 and 84. There were no differences between INFLAM and CON gilts litter mortality outcomes (P ≥ 0.13), but INFLAM pigs were smaller (P = 0.04) at birth and tended (P = 0.09) to be smaller at weaning. Muscle and organ weights did not differ (P ≥ 0.17) between treatments, with the exception of semitendinosus, which was smaller (P < 0.01) in INFLAM pigs. INFLAM pigs tended (P = 0.06) to have larger type I fibers. INFLAM pig TNF-α concentration did not differ across time, while CON pig TNF-α concentration peaked (P = 0.01) 4 h postinjection. TNF-α concentration did not differ between treatments at 0 and 8 h postinjection, but CON pigs had increased (P = 0.01) TNF-α compared to INFLAM pigs 4 h postinjection. Overall, maternal immune activation did not alter pig muscle development, but resulted in suppressed innate immune activation.

摘要

目的是确定母体炎症对后代肌肉发育和产后先天免疫反应的影响。将 16 头初产母猪随机分为重复静脉内注射脂多糖(LPS;n = 8,处理代码 INFLAM)或可比体积的磷酸盐缓冲盐水(CON,n = 8)。从妊娠第 70 天(GD)到第 84 天,每隔一天进行一次注射,初始剂量为 10μg LPS/kg 体重(BW),每次增加 12%,以防止内毒素耐受。在 GD 70、76 和 84 时,通过颈静脉或耳静脉穿刺在注射后 0 和 4 小时采集血液,以确定肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6 和 IL-1β浓度。分娩后,记录死产,并选择最接近窝 BW 平均值的仔猪进行解剖和肌肉纤维特征分析。断奶时(产后第 21 天),对仔猪进行单独称重,并选择最接近窝 BW 平均值的 2 头公猪进行另一项研究。选择第三头最接近窝 BW 平均值的公猪进行产后 LPS 挑战。在 PND 52 时,通过腹腔内注射给仔猪 5μg LPS/kg BW,在注射后 0、4 和 8 小时采集血液,以确定 TNF-α浓度。INFLAM 母猪的 TNF-α浓度在注射后 4 小时(P < 0.01)比注射后 0 小时增加,而 CON 母猪的 TNF-α浓度在两个时间点之间没有差异。INFLAM 母猪的 IL-6 和 IL-1β浓度在注射后 4 小时(P = 0.03)比注射后 0 小时增加,但在 GD 76 和 84 时两个时间点之间没有差异。INFLAM 和 CON 母猪的产仔死亡率结果没有差异(P≥0.13),但 INFLAM 仔猪出生时较小(P = 0.04),断奶时倾向于较小(P = 0.09)。处理之间肌肉和器官重量没有差异(P≥0.17),除半腱肌外,INFLAM 仔猪的半腱肌较小(P < 0.01)。INFLAM 仔猪的 I 型纤维倾向于较大(P = 0.06)。INFLAM 仔猪的 TNF-α浓度在不同时间没有差异,而 CON 仔猪的 TNF-α浓度在注射后 4 小时达到峰值(P = 0.01)。TNF-α浓度在注射后 0 和 8 小时在处理之间没有差异,但 CON 仔猪的 TNF-α浓度在注射后 4 小时比 INFLAM 仔猪高(P = 0.01)。总体而言,母体免疫激活并未改变猪的肌肉发育,但导致先天免疫激活受到抑制。

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