Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
Master Program in Food Safety, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
JPEN J Parenter Enteral Nutr. 2019 Sep;43(7):927-936. doi: 10.1002/jpen.1505. Epub 2019 Feb 4.
Sepsis is a syndrome with CD4 T-cell dysfunction and dysregulation of T helper (Th) and regulatory T (Treg) cells. Glutamine (Gln) is a nutrient with immunomodulatory properties. This study investigated the effects of dietary Gln pretreatment on Th and Treg cell homeostasis and lung injury in mice with gut-derived polymicrobial sepsis.
Mice were randomly assigned to 4 groups with 2 control (C and G) and 2 sepsis groups (SC and SG). The C and SC groups were fed a common semipurified diet, whereas the G and SG groups received an identical diet except that part of the casein was replaced by Gln. Mice were administered these diets for 2 weeks. Then mice in the control groups underwent a sham operation, whereas operations in the sepsis groups were performed with cecal ligation and puncture. Mice were killed 24 hours after the surgery. Blood, spleens, and lungs were collected for further examination.
Sepsis resulted in a decreased blood T-lymphocyte percentage, whereas percentages of interferon-γ-expressing, interleukin (IL)-4-expressing, and IL-17-expressing CD4 T cells were upregulated. Compared with the SC group, Gln administration before sepsis reduced blood Th1, Th2, and Th17 but increased Treg percentages. Also, percentages of CD69-expressing CD4 and CD8 cells in the spleen increased. Concomitant with the decreased plasma IL-6 and keratinocyte-derived chemokine levels, the SG group exhibited a lower injury score of the lungs.
Pretreatment with Gln may elicit more balanced Th polarization, alleviate inflammatory response, and attenuate lung injury induced by polymicrobial sepsis.
败血症是一种伴有 CD4 T 细胞功能障碍以及辅助性 T（Th）和调节性 T（Treg）细胞失调的综合征。谷氨酰胺（Gln）是一种具有免疫调节特性的营养物质。本研究旨在探讨肠源性多微生物败血症小鼠中，膳食 Gln 预处理对 Th 和 Treg 细胞稳态及肺损伤的影响。
将小鼠随机分为 4 组，包括 2 个对照组（C 和 G）和 2 个败血症组（SC 和 SG）。C 和 SC 组给予常规半纯化饮食，而 G 和 SG 组给予相同的饮食，只是部分酪蛋白被 Gln 替代。小鼠接受这些饮食 2 周。然后对照组小鼠接受假手术，而败血症组小鼠接受盲肠结扎和穿刺手术。术后 24 小时处死小鼠，收集血液、脾脏和肺脏进行进一步检查。
败血症导致血 T 淋巴细胞百分比降低，而干扰素-γ表达、白细胞介素（IL）-4 表达和 IL-17 表达的 CD4 T 细胞百分比升高。与 SC 组相比，败血症前给予 Gln 可降低血 Th1、Th2 和 Th17 细胞百分比，增加 Treg 细胞百分比。此外，脾脏中 CD69 表达的 CD4 和 CD8 细胞的百分比也增加。与血浆 IL-6 和角质形成细胞衍生趋化因子水平降低相一致，SG 组的肺部损伤评分较低。
Gln 预处理可引起更平衡的 Th 极化，减轻炎症反应，并减轻多微生物败血症引起的肺损伤。
