Institute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.
Institute of Behavioural Physiology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.
Int J Mol Sci. 2019 Mar 20;20(6):1393. doi: 10.3390/ijms20061393.
Although dexamethasone (DEX) is a widely used immunoregulatory agent, knowledge about its pharmacological properties in farm animals, especially pigs, is insufficient. Previous studies suggest that compared to other species, pigs are less sensitive to the immunosuppression conferred by DEX and more sensitive to the threat of bacterial endotoxins. However, there is a paucity of studies examining DEX immunomodulation in endotoxemia in this species. In this study, a porcine endotoxemia model was established by lipopolysaccharide (LPS) and the effect of DEX-pretreatment on the magnitude and kinetics of neuroendocrine, metabolic, hematologic, inflammatory, and behavioural responses were examined. DEX decreased cortisol, adrenocorticotropic hormone (ACTH), red blood cell, hemoglobin, hematocrit, and lymphocyte whereas glucose concentration was increased under both normal and endotoxemic conditions. By contrast, DEX decreased triglyceride, lactate, and IL-6 concentrations and increased platelet count only under an endotoxemic condition. DEX also reduced the frequency of sickness behaviour following LPS challenge. PCA showed that glucose and triglyceride metabolism together with red blood cell count mainly contributed to the separation of clusters during DEX treatment. Our study demonstrates that DEX protects pigs from inflammation and morbidity in endotoxemia, in spite of their less sensitivity to DEX. Moreover, its considerable role in the regulation of the metabolic and hematologic responses in endotoxemic pigs is revealed for the first time.
尽管地塞米松(DEX)是一种广泛使用的免疫调节剂,但关于其在农场动物(尤其是猪)中的药理学特性的知识还不够充分。先前的研究表明,与其他物种相比,猪对 DEX 引起的免疫抑制作用的敏感性较低,而对细菌内毒素的威胁的敏感性较高。然而,在这种物种中,很少有研究检查 DEX 在内毒素血症中的免疫调节作用。在本研究中,通过脂多糖(LPS)建立了猪内毒素血症模型,并检查了 DEX 预处理对内分泌、代谢、血液、炎症和行为反应的幅度和动力学的影响。DEX 降低了皮质醇、促肾上腺皮质激素(ACTH)、红细胞、血红蛋白、血细胞比容和淋巴细胞,而在正常和内毒素血症条件下葡萄糖浓度增加。相比之下,DEX 仅在内毒素血症条件下降低了甘油三酯、乳酸和 IL-6 浓度并增加了血小板计数。DEX 还降低了 LPS 挑战后的疾病行为频率。PCA 表明,葡萄糖和甘油三酯代谢以及红细胞计数主要有助于 DEX 治疗期间簇的分离。我们的研究表明,DEX 可保护猪免受内毒素血症中的炎症和发病,尽管它们对 DEX 的敏感性较低。此外,首次揭示了其在调节内毒素血症猪的代谢和血液反应中的重要作用。