Citrulline supplementation exacerbates sepsis severity in infected preterm piglets via early induced immunosuppression

IF 4.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Nutritional Biochemistry Pub Date : 2024-05-31 DOI:10.1016/j.jnutbio.2024.109674
Jingren Zhong , Sebastian Høj Johansen , Ole Bæk , Duc Ninh Nguyen
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Abstract

Arginine (ARG)/Citrulline (CIT) deficiency is associated with increased sepsis severity after infection. Supplementation of CIT to susceptible patients with ARG/CIT deficiency such as preterm newborns with suspected infection might prevent sepsis, via maintaining immune and vascular function. Caesarean-delivered, parenterally nourished preterm pigs were treated with CIT (1g/kg bodyweight) via oral or continuous intravenous supplementation, then inoculated with live Staphylococcus epidermidis and clinically monitored for 14 h. Blood, liver, and spleen samples were collected for analysis. In vitro cord blood stimulation was performed to explore how CIT and ARG affect premature blood cell responses. After infection, oral CIT supplementation led to higher mortality, increased blood bacterial load, and systemic and hepatic inflammation. Intravenous CIT administration showed increased inflammation and bacterial burdens without significantly affecting mortality. Liver transcriptomics and data from in vitro blood stimulation indicated that CIT induces systemic immunosuppression in preterm newborns, which may impair resistance response to bacteria at the early stage of infection, subsequently causing later uncontrollable inflammation and tissue damage. The early stage of CIT supplementation exacerbates sepsis severity in infected preterm pigs, likely via inducing systemic immunosuppression.

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通过早期诱导免疫抑制,补充瓜氨酸会加剧感染早产仔猪败血症的严重程度。
背景:精氨酸(ARG)/瓜氨酸(CIT)缺乏与感染后败血症严重程度增加有关。向缺乏 ARG/CIT 的易感人群(如疑似感染的早产新生儿)补充 CIT 可通过维持免疫和血管功能来预防败血症:方法:通过口服或持续静脉注射 CIT(1 克/千克),对剖腹产的亲喂早产猪进行治疗,然后接种活的表皮葡萄球菌,并进行 14 小时的临床监测。收集血液、肝脏和脾脏样本进行分析。对脐带血进行体外刺激,以探索 CIT 和 ARG 如何影响早老性血细胞反应:结果:感染后,口服 CIT 会导致死亡率升高、血液细菌负荷增加以及全身和肝脏炎症。静脉注射 CIT 会增加炎症和细菌负荷,但不会显著影响死亡率。肝脏转录组学和体外血液刺激的数据表明,CIT会诱导早产新生儿的全身免疫抑制,这可能会在感染早期损害对细菌的抵抗反应,随后导致无法控制的炎症和组织损伤:结论:补充 CIT 的早期阶段会加剧感染早产猪的败血症严重程度,这可能是通过诱导全身免疫抑制造成的。
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来源期刊
Journal of Nutritional Biochemistry
Journal of Nutritional Biochemistry 医学-生化与分子生物学
CiteScore
9.50
自引率
3.60%
发文量
237
审稿时长
68 days
期刊介绍: Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology. Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.
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