Elsasser T H, Caperna T J, Li C-J, Kahl S, Sartin J L
United States Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705, USA.
J Anim Sci. 2008 Apr;86(14 Suppl):E105-25. doi: 10.2527/jas.2007-0634. Epub 2008 Mar 14.
Intrinsic in the equation for successful animal production is the efficiency of nutrient use for assimilation into useful animal-derived products. However, when young growing animals encounter various stressors that activate the proinflammatory response (PR), the biochemical effects of the resulting cascade of PR mediators [cytokines, prostaglandin and prosta-cyclin derivatives, nitric oxide (NO), superoxide anion (O2(.-)), etc.] override the regulatory signals normally ascribed to anabolic tissue accretion and growth. The efficiency of energy and nutrient use will proportionally decrease for growth rate due to the redirection of nutrient use to support immune defense processes. These proinflammatory events can develop in association with infectious disease but also are apparent in and a part of the natural response to birth, parturition, and weaning. If growth patterns are tracked during the PR, growth deficits are often apparent. Some growth deficits are relatively transient in duration, whereas others are quite long lasting, persisting although traditional clinical markers of PR are no longer evident. Recent evidence indicates that the PR cascades initiated by cytokines like tumor necrosis factor-alpha play a major role in these growth deficits. Perturbations in mitochondrial energetics and NO and O2(.-) interactions further affect metabolic balance. Free radicals and reactive nitrogen intermediates interact with select molecular targets in proteins (i.e., enzymes, histone proteins, and signal transduction proteins), causing the nitration and nitrosylation of select amino acids. If these posttranslational modifications occur in proteins associated with control points critical in metabolic stability, the resulting altered protein structure blocks its functionality. Attenuation of these overt posttranslational protein modifications at their site of production offers a strategy to minimize their detrimental impact while preserving needed cytokine, NO, and O2(.-) functions.
成功进行动物生产的方程式的内在因素是营养物质用于同化形成有用动物衍生产品的效率。然而，当幼年生长动物遇到各种激活促炎反应（PR）的应激源时，由此产生的PR介质级联反应[细胞因子、前列腺素和前列环素衍生物、一氧化氮（NO）、超氧阴离子（O2(.-)）等]的生化作用会超越通常归因于合成代谢组织增生和生长的调节信号。由于营养物质被重新导向以支持免疫防御过程，能量和营养物质的利用效率将随着生长速率成比例下降。这些促炎事件可能与传染病相关，但在出生、分娩和断奶的自然反应中也很明显，并且是其中的一部分。如果在PR期间跟踪生长模式，生长缺陷通常很明显。一些生长缺陷持续时间相对较短，而另一些则持续时间很长，尽管PR的传统临床指标不再明显，但仍会持续存在。最近的证据表明，由肿瘤坏死因子-α等细胞因子引发的PR级联反应在这些生长缺陷中起主要作用。线粒体能量学以及NO和O2(.-)相互作用的扰动进一步影响代谢平衡。自由基和活性氮中间体与蛋白质中的特定分子靶点（即酶、组蛋白和信号转导蛋白）相互作用，导致特定氨基酸的硝化和亚硝化。如果这些翻译后修饰发生在与代谢稳定性关键控制点相关的蛋白质中，由此改变的蛋白质结构会阻碍其功能。在其产生部位减弱这些明显的翻译后蛋白质修饰提供了一种策略，可在保留所需细胞因子、NO和O2(.-)功能的同时，将其有害影响降至最低。
