Lipid and Lipoprotein Dysregulation in Sepsis: Clinical and Mechanistic Insights into Chronic Critical Illness.
Lipid and Lipoprotein Dysregulation in Sepsis: Clinical and Mechanistic Insights into Chronic Critical Illness.
复制标题
DOI：
10.3390/jcm10081693
复制
发表时间：
2021-04-14
影响因子：
3.9
通讯作者：
Guirgis FW
中科院分区：
文献类型：
--
作者：
Barker G;Leeuwenburgh C;Brusko T;Moldawer L;Reddy ST;Guirgis FW
除了它们在代谢中的充分表征的作用之外，脂质和脂蛋白对先天免疫系统具有多效性作用。这些在脓毒症和急性炎症反应期间发生临床相关的改变。高密度脂蛋白（HDL）通过清除细菌毒素、支持皮质类固醇释放、减少血小板聚集、抑制内皮细胞凋亡、减轻单核细胞炎症反应、抑制内皮细胞粘附分子的表达等，在免疫调节中发挥重要作用。它经历了定量和定性的变化，可以使用HDL炎症指数（HII）进行测量。促炎性或功能障碍性HDL（dysHDL）缺乏执行这些功能的能力，我们还发现它可以独立预测脓毒症的不良结局和器官衰竭。另一类重要的脂质被称为特化促消退介质（SPMs），以时间方式积极影响炎症的升级和消退。这些在脓毒症中经历表型变化，并且在幸存者和非幸存者之间显著不同。败血症幸存者的某些子集继续具有危险的住院后病程，其中这种炎症以低度方式继续。这与持续性炎症、免疫抑制和卡他综合征（PICS）综合征中的免疫抑制有关。组织损伤相关模式的持续释放和继发于免疫抑制的病毒再激活助长了这种慢性炎症循环。动物数据表明，内源性脂质和SPM的失调在这一过程中发挥重要作用。近年来，脂质及其相关途径一直是许多临床试验的目标，但这些试验并未显示死亡率获益。这些结果受到患者异质性和较差动物模型的限制。脓毒症表型和新的生物标志物在未来的试验中的考虑是未来研究中需要考虑的重要因素。脓毒症期间脂质失调和慢性炎症的进一步表征将有助于死亡风险分层、脓毒症的检测，并为个体化药物治疗提供信息。
In addition to their well-characterized roles in metabolism, lipids and lipoproteins have pleiotropic effects on the innate immune system. These undergo clinically relevant alterations during sepsis and acute inflammatory responses. High-density lipoprotein (HDL) plays an important role in regulating the immune response by clearing bacterial toxins, supporting corticosteroid release, decreasing platelet aggregation, inhibiting endothelial cell apoptosis, reducing the monocyte inflammatory response, and inhibiting expression of endothelial cell adhesion molecules. It undergoes quantitative as well as qualitative changes which can be measured using the HDL inflammatory index (HII). Pro-inflammatory, or dysfunctional HDL (dysHDL) lacks the ability to perform these functions, and we have also found it to independently predict adverse outcomes and organ failure in sepsis. Another important class of lipids known as specialized pro-resolving mediators (SPMs) positively affect the escalation and resolution of inflammation in a temporal fashion. These undergo phenotypic changes in sepsis and differ significantly between survivors and non-survivors. Certain subsets of sepsis survivors go on to have perilous post-hospitalization courses where this inflammation continues in a low grade fashion. This is associated with immunosuppression in a syndrome of persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The continuous release of tissue damage-related patterns and viral reactivation secondary to immunosuppression feed this chronic cycle of inflammation. Animal data indicate that dysregulation of endogenous lipids and SPMs play important roles in this process. Lipids and their associated pathways have been the target of many clinical trials in recent years which have not shown mortality benefit. These results are limited by patient heterogeneity and poor animal models. Considerations of sepsis phenotypes and novel biomarkers in future trials are important factors to be considered in future research. Further characterization of lipid dysregulation and chronic inflammation during sepsis will aid mortality risk stratification, detection of sepsis, and inform individualized pharmacologic therapies.
登录
查看更多内容
影响因子：
2.7
作者：
Cámara-Lemarroy CR;Guzman-DE LA Garza FJ;Cordero-Perez P;Ibarra-Hernandez JM;Muñoz-Espinosa LE;Fernandez-Garza NE
通讯作者：
Fernandez-Garza NE
影响因子：
4.6
作者：
Al-Banna N;Lehmann C
通讯作者：
Lehmann C
影响因子：
4.5
作者：
Burillo, Elena;Mateo-Gallego, Rocio;Civeira, Fernando
通讯作者：
Civeira, Fernando
影响因子：
9
作者：
Brakenridge, Scott C.;Efron, Philip A.;Moore, Frederick A.
通讯作者：
Moore, Frederick A.
影响因子：
4.8
作者：
Cavigiolio, Giorgio;Geier, Ethan G.;Oda, Michael N.
通讯作者：
Oda, Michael N.