Age-dependent alterations in the inflammatory response to pulmonary challenge.
Age-dependent alterations in the inflammatory response to pulmonary challenge.
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DOI：
10.1007/s12026-015-8684-7
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发表时间：
2015-12
影响因子：
4.4
通讯作者：
Miller EJ
中科院分区：
文献类型：
--
作者：
Linge HM;Ochani K;Lin K;Lee JY;Miller EJ
老化的肺部越来越容易感染传染病。肺部生理和功能的变化在老年人群中很常见，而在 60 岁以上的人群中，肺炎是感染性死亡的主要原因。了解先天性和适应性免疫系统中与年龄相关的变化，以及它们如何影响肺部和全身对肺部挑战的反应，对于开发治疗老年患者的新治疗策略至关重要。在这项观察性研究中，我们研究了革兰氏阳性菌细胞壁成分对肺部攻击的炎症反应与年龄相关的差异。因此，对 6 个月或 18 个月以上的雄性 Sprague-Dawley 大鼠（近似人类 20 岁和 55-65 岁）进行气管内注射脂磷壁酸和肽聚糖的攻击。攻击后 24 小时，对支气管肺泡灌洗液 (BAL) 和血浆进行细胞和细胞因子评估。还评估了游离甲状腺素的血浆浓度，这是非甲状腺疾病严重程度的标志。年长的动物有利于空域的趋化梯度增加，这与中性粒细胞和蛋白质的更多积累有关。此外，巨噬细胞迁移抑制因子 (MIF)（一种炎症介质和急性肺损伤的假定生物标志物）在老年动物的血浆和 BAL 中增加，但在年轻动物中则没有增加。相反，老年动物中血浆游离甲状腺素（MIF 的天然抑制剂）减少。这些发现确定了肺部挑战后与年龄相关的炎症/代谢变化，可以通过操纵来改善老年危重患者的预后。
The aging lung is increasingly susceptible to infectious disease. Changes in pulmonary physiology and function are common in older populations, and in those older than 60 years, pneumonia is the major cause of infectious death. Understanding age-related changes in the innate and adaptive immune systems, and how they affect both pulmonary and systemic responses to pulmonary challenge are critical to the development of novel therapeutic strategies for the treatment of the elderly patient. In this observational study, we examined age-associated differences in inflammatory responses to pulmonary challenge with cell wall components from Gram-positive bacteria. Thus, male Sprague–Dawley rats, aged 6 months or greater than 18 months (approximating humans of 20 and 55–65 years), were challenged, intratracheally, with lipoteichoic acid and peptidoglycan. Cellular and cytokine evaluations were performed on both bronchoalveolar lavage fluid (BAL) and plasma, 24 h post-challenge. The plasma concentration of free thyroxine, a marker of severity in non-thyroidal illness, was also evaluated. The older animals had an increased chemotactic gradient in favor of the airspaces, which was associated with a greater accumulation of neutrophils and protein. Furthermore, macrophage migration inhibitory factor (MIF), an inflammatory mediator and putative biomarker in acute lung injury, was increased in both the plasma and BAL of the older, but not young animals. Conversely, plasma free thyroxine, a natural inhibitor of MIF, was decreased in the older animals. These findings identify age-associated inflammatory/metabolic changes following pulmonary challenge that it may be possible to manipulate to improve outcome in the older, critically ill patient.