IL-27 is elevated in sepsis with acute hepatic injury and promotes hepatic damage and inflammation in the CLP model

• Published in: Cytokine (Philadelphia, Pa.) Vol. 127; p. 154936
• Main Authors: Fan, Jing, Zhang, Yu-chi, Zheng, Dao-feng, Zhang, Mu, Liu, Hang, He, Miao, Wu, Zhong-jun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2020
• Subjects: Acute hepatic injury; Immune response; Inflammation; Interleukin-27; Sepsis; PCT; CRP; AHI; SAAHI; CLP; JNK; EBI3; ALT; WSX-1/TCCR; TNF; LPS; Acute hepatic injury; MODS; WBC; WT; ARDS; AST; Immune response; IL; Inflammation; SOFA; Sepsis; Interleukin-27; SNHI; APACHE
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2019.154936

•IL-27 is elevated in sepsis patient with acute hepatic injury.•IL-27 can promote inflammatory reaction in CLP-induced hepatic injury mice model.•IL-27 might involve in the activation of p-JNK in macrophages.•IL-27 promote pro-inflammation cytokines production in macrophages. 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. 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. 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. 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.