Woodward Bill
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
Int J Mol Sci. 2016 Apr 11;17(4):541. doi: 10.3390/ijms17040541.
Inflammatory incompetence is characteristic of acute pediatric protein-energy malnutrition, but its underlying mechanisms remain obscure. Perhaps substantially because the research front lacks the driving force of a scholarly unifying hypothesis, it is adrift and research activity is declining. A body of animal-based research points to a unifying paradigm, the Tolerance Model, with some potential to offer coherence and a mechanistic impetus to the field. However, reasonable skepticism prevails regarding the relevance of animal models of acute pediatric malnutrition; consequently, the fundamental contributions of the animal-based component of this research front are largely overlooked. Design-related modifications to improve the relevance of animal modeling in this research front include, most notably, prioritizing essential features of pediatric malnutrition pathology rather than dietary minutiae specific to infants and children, selecting windows of experimental animal development that correspond to targeted stages of pediatric immunological ontogeny, and controlling for ontogeny-related confounders. In addition, important opportunities are presented by newer tools including the immunologically humanized mouse and outbred stocks exhibiting a magnitude of genetic heterogeneity comparable to that of human populations. Sound animal modeling is within our grasp to stimulate and support a mechanistic research front relevant to the immunological problems that accompany acute pediatric malnutrition.
炎症功能不全是小儿急性蛋白质 - 能量营养不良的特征，但其潜在机制仍不清楚。很大程度上可能是因为该研究前沿缺乏一个学术统一假说的驱动力，从而处于漂泊不定的状态，研究活动也在减少。一系列基于动物的研究指向了一个统一范式——耐受模型，它有潜力为该领域提供连贯性和机制性推动。然而，对于小儿急性营养不良动物模型的相关性存在合理的怀疑；因此，这一研究前沿中基于动物部分的基础性贡献在很大程度上被忽视了。为提高该研究前沿中动物模型的相关性而进行的与设计相关的改进包括，最显著的是，优先考虑小儿营养不良病理学的基本特征，而不是婴幼儿特有的饮食细节，选择与小儿免疫发育的目标阶段相对应的实验动物发育窗口，并控制与发育相关的混杂因素。此外，包括免疫人源化小鼠和表现出与人类群体相当程度遗传异质性的远交系在内的新工具带来了重要机遇。合理的动物模型构建在我们的掌控之中，以刺激和支持与小儿急性营养不良伴随的免疫问题相关的机制性研究前沿。
