BACKGROUND Immuno-inflammation plays an important role in the pathophysiological process of sepsis-associated acute hepatic injury (AHI). Interleukin 27 (IL-27) is an important inflammatory regulator; however, its role in this condition is not clear. METHODS The clinical data and IL-27 serum levels in sepsis patients with or without AHI were analysed. Classical caecal ligation puncture (CLP) models were established in wild-type (WT) and IL-27 receptor (WSX-1)-deficient (IL-27R-/-) mice. In addition, exogenous IL-27 was injected into these mice, and the levels of IL-27, IL-6, and tumour necrosis factor alpha (TNF-α) in the serum and liver were then measured by enzyme-linked immunoassay (ELISA), quantitative PCR, and Western blotting. The severity of liver damage was evaluated by haematoxylin and eosin staining of liver tissue, TUNEL assay and evaluation of alanine aminotransferase (ALT) and aspartate transaminase (AST) serum levels. Furthermore, the effects of IL-27 on the levels of phosphorylated c-Jun N-terminal kinase (JNK) in macrophages were assessed by Western blotting, and the effects of IL-27 on the expression of IL-6 and TNF-α in macrophages were assessed by ELISA. RESULTS IL-27 was elevated in sepsis patients with acute hepatic injury, which correlated with the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHEII) scores, Sequential Organ Failure Assessment (SOFA) scores, and procalcitonin, C-reactive protein, IL-6, and TNF-α expression. In the CLP-WT group, IL-27 was highly expressed in the serum and liver, which correlated with the elevated content of ALT, AST, TNF-α, IL-6, and p-JNK in the serum and liver and the pathological injury of the liver. In CLP-IL-27R-/- group, however, the levels of ALT, AST, TNF-α, IL-6, and p-JNK in the serum and liver and the pathological injury of the liver were decreased. Treatment with exogenous IL-27 led to a further increase in these cytokines in WT mice after CLP. IL-27 treatment and lipopolysaccharide stimulation in vitro increased the expression of p-JNK, IL-6, and TNF-α in macrophages, and these changes were decreased by a JNK signalling pathway inhibitor. CONCLUSION IL-27 is elevated in sepsis patients, especially those with acute hepatic injury. In addition, IL-27 can promote inflammatory reactions in the CLP-induced hepatic injury mice model.

中文翻译：

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IL-27 在脓毒症伴急性肝损伤中升高，并在 CLP 模型中促进肝损伤和炎症

背景免疫炎症在脓毒症相关急性肝损伤(AHI)的病理生理过程中起重要作用。白细胞介素 27 (IL-27) 是一种重要的炎症调节剂；然而，它在这种情况下的作用尚不清楚。方法分析合并或不合并AHI的脓毒症患者的临床资料和血清IL-27水平。在野生型 (WT) 和 IL-27 受体 (WSX-1) 缺陷 (IL-27R-/-) 小鼠中建立了经典的盲肠结扎穿刺 (CLP) 模型。此外，将外源性IL-27注射到这些小鼠体内，然后通过酶联免疫分析（ELISA）测量血清和肝脏中IL-27、IL-6和肿瘤坏死因子α（TNF-α）的水平。 )、定量 PCR 和蛋白质印迹。通过肝组织苏木精和伊红染色评估肝损伤的严重程度，TUNEL 测定和评估丙氨酸转氨酶 (ALT) 和天冬氨酸转氨酶 (AST) 血清水平。此外，通过蛋白质印迹评估 IL-27 对巨噬细胞中磷酸化 c-Jun N-末端激酶 (JNK) 水平的影响，以及 IL-27 对巨噬细胞中 IL-6 和 TNF-α 表达的影响。通过ELISA评估巨噬细胞。结果 急性肝损伤脓毒症患者 IL-27 升高，这与急性生理评估和慢性健康评估 II (APACHEII) 评分、序贯器官衰竭评估 (SOFA) 评分和降钙素原、C 反应蛋白、IL- 6、TNF-α的表达。在 CLP-WT 组中，IL-27 在血清和肝脏中高表达，这与 ALT、AST、TNF-α、IL-6、血清和肝脏中的p-JNK及肝脏病理损伤。CLP-IL-27R-/-组血清和肝脏中ALT、AST、TNF-α、IL-6、p-JNK水平降低，肝脏病理损伤降低。用外源性 IL-27 治疗导致 CLP 后 WT 小鼠中这些细胞因子的进一步增加。IL-27 处理和体外脂多糖刺激增加了巨噬细胞中 p-JNK、IL-6 和 TNF-α 的表达，而 JNK 信号通路抑制剂可降低这些变化。结论 IL-27 在脓毒症患者中升高，尤其是急性肝损伤患者。此外，IL-27 可以促进 CLP 诱导的肝损伤小鼠模型的炎症反应。血清和肝脏中的p-JNK及肝脏病理损伤均降低。用外源性 IL-27 治疗导致 CLP 后 WT 小鼠中这些细胞因子的进一步增加。IL-27 处理和体外脂多糖刺激增加了巨噬细胞中 p-JNK、IL-6 和 TNF-α 的表达，而 JNK 信号通路抑制剂可降低这些变化。结论 IL-27 在脓毒症患者中升高，尤其是急性肝损伤患者。此外，IL-27 可以促进 CLP 诱导的肝损伤小鼠模型的炎症反应。血清和肝脏中的p-JNK及肝脏病理损伤均降低。用外源性 IL-27 治疗导致 CLP 后 WT 小鼠中这些细胞因子的进一步增加。IL-27 处理和体外脂多糖刺激增加了巨噬细胞中 p-JNK、IL-6 和 TNF-α 的表达，而 JNK 信号通路抑制剂可降低这些变化。结论 IL-27 在脓毒症患者中升高，尤其是急性肝损伤患者。此外，IL-27 可以促进 CLP 诱导的肝损伤小鼠模型的炎症反应。并且这些变化被 JNK 信号通路抑制剂减少了。结论 IL-27 在脓毒症患者中升高，尤其是急性肝损伤患者。此外，IL-27 可以促进 CLP 诱导的肝损伤小鼠模型的炎症反应。并且这些变化被 JNK 信号通路抑制剂减少了。结论 IL-27 在脓毒症患者中升高，尤其是急性肝损伤患者。此外，IL-27 可以促进 CLP 诱导的肝损伤小鼠模型的炎症反应。