Role of interleukin-23 in monocyte-derived dendritic cells of HBV-related acute-on-chronic liver failure and its correlation with the severity of liver damage

Background: The role of interleukin-23 (IL-23) in monocyte-derived dendritic cells (MoDCs) from hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients remains unclear. The aim of this study was to observe the correlation between the activation of the IL-23 signaling pathway and the prognosis of HBV-ACLF patients. Materials and methods: The baseline levels of serum IL-6, IL-12, IL-17, IL-23, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) from immune tolerant (IT), chronic hepatitis B (CHB), HBV-ACLF patients and healthy individuals who served as healthy controls (HCs) were analyzed using the Luminex system, whereas serum IL-23 from HBV-ACLF patients was measured by ELISA before and after treatment. Purified monocytes were isolated from peripheral blood and were induced into MoDCs, IL-23, IL-23R, NF-kappa B and TRAF6 expression in MoDCs from 4 groups was analyzed using real-time PCR, and IL-23R and intracellular IL-23 were evaluated by flow cytometry. Results: Serum IL-6, IL-12, IL-17, IL-23 and TNF-alpha levels were upregulated in HBV-ACLF patients compared with IT patients, CHB patients and HCs (P < 0.05 for all). Serum IL-23 was closely correlated with elevated serum IL-17 in HBV-ACLF patients (r = 0.5935, P < 0.0001). Moreover, IL-23 and IL-23R levels were significantly upregulated in MoDCs from patients with CHB or HBV-ACLF compared with HCs, and further upregulation of IL-23 and IL-23R was observed in HBV-ACLF patients compared to CHB patients (P < 0.05 for all). IL-23 expression was markedly enhanced and was correlated with elevated NF-kappa B and TRAF6 in MoDCs from HBV-ACLF patients ( P < 0.05 for both). Linear correlation analysis demonstrated significant correlations between the expression of IL-23 and disease severity markers (MELD scoring system, international normalized ratio, prothrombin time and total bilirubin, r = 0.6874, r = 0.6475, r = 0.6249, r = 0.3771, respectively, P < 0.05 for all) for individual HBV-ACLF patients, and IL-23 levels were significantly upregulated in non-survival HBV-ACLF patients compared with survival HBV-ACLF patients ( P < 0.05). Conclusion: IL-23 in serum and MoDCs is significantly elevated in HBV-ACLF patients, TRAF6/NF-kappa B may play a role in IL-23 production by MoDCs in HBV-ACLF patients and high pre-treatment IL-23 levels in MoDCs are associated with mortality in HBV-ACLF patients. (C) 2016 Elsevier Masson SAS. All rights reserved.