Department of Animal Sciences and Industry, Kansas State University,1530 Mid-Campus Dr. N., Manhattan, KS66506, USA.
Animal. 2020 Mar;14(S1):s144-s154. doi: 10.1017/S1751731119003203.
Inflammatory cascades are a critical component of the immune response to infection or tissue damage, involving an array of signals, including water-soluble metabolites, lipid mediators and several classes of proteins. Early investigation of these signaling pathways focused largely on immune cells and acute disease models. However, more recent findings have highlighted critical roles of both immune cells and inflammatory mediators on tissue remodeling and metabolic homeostasis in healthy animals. In dairy cattle, inflammatory signals in various tissues and in circulation change rapidly and dramatically, starting just prior to and at the onset of lactation. Furthermore, several observations in healthy cows point to homeostatic control of inflammatory tone, which we define as a regulatory process to balance immune tolerance with activation to keep downstream effects under control. Recent evidence suggests that peripartum inflammatory changes influence whole-body nutrient flux of dairy cows over the course of days and months. Inflammatory mediators can suppress appetite, even at levels that do not induce acute responses (e.g. fever), thereby decreasing nutrient availability. On the other hand, inhibition of inflammatory signaling with non-steroidal anti-inflammatory drug (NSAID) treatment suppresses hepatic gluconeogenesis, leading to hypoglycemia in some cases. Over the long term, though, peripartum NSAID treatment substantially increases peak and whole-lactation milk synthesis by multiparous cows. Inflammatory regulation of nutrient flux may provide a homeorhetic mechanism to aid cows in adapting to rapid changes in metabolic demand at the onset of lactation, but excessive systemic inflammation has negative effects on metabolic homeostasis through inhibition of appetite and promotion of immune cell activity. Thus, in this review, we provide perspectives on the overlapping regulation of immune responses and metabolism by inflammatory mediators, which may provide a mechanistic underpinning for links between infectious and metabolic diseases in transition dairy cows. Moreover, we point to novel approaches to the management of this challenging phase of the production cycle.
炎症级联反应是机体对感染或组织损伤的免疫反应的一个关键组成部分，涉及一系列信号，包括水溶性代谢物、脂质介质和几类蛋白质。早期对这些信号通路的研究主要集中在免疫细胞和急性疾病模型上。然而，最近的研究结果强调了免疫细胞和炎症介质在健康动物组织重塑和代谢稳态中的关键作用。在奶牛中，各种组织和循环中的炎症信号在泌乳开始前和开始时迅速而显著地变化。此外，在健康奶牛中的几项观察结果表明，炎症反应的动态平衡控制，我们将其定义为一种平衡免疫耐受与激活的调节过程，以控制下游效应。最近的证据表明，围产期炎症变化会影响奶牛在数天和数月内的全身营养通量。炎症介质可以抑制食欲，即使在不会引起急性反应（如发烧）的水平，从而减少营养物质的可用性。另一方面，非甾体抗炎药（NSAID）治疗抑制炎症信号通路会抑制肝脏的糖异生，导致某些情况下出现低血糖。然而，从长远来看，围产期 NSAID 治疗会显著增加经产奶牛的高峰和整个泌乳期的产奶量。炎症对营养通量的调节可能为奶牛在泌乳开始时适应代谢需求的快速变化提供了一种同源调节机制，但过度的全身炎症通过抑制食欲和促进免疫细胞活性对代谢稳态产生负面影响。因此，在这篇综述中，我们提供了炎症介质对免疫反应和代谢的重叠调节的观点，这可能为处于过渡阶段的奶牛的传染性和代谢性疾病之间的联系提供了一种机制基础。此外，我们还指出了管理这一生产周期具有挑战性阶段的新方法。
