NLRP3 inflammasome and related cytokines reflect the immune status of patients with HBV-ACLF

• Published in: Molecular immunology Vol. 120; pp. 179 - 186
• Main Authors: Jia, Yanhong, Ma, Luyuan, Wang, Yadong, Wang, Wei, Shen, Chuan, Wang, Xin, Xu, Hongrui, Zhao, Caiyan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2020
• Subjects: Acute-on-Chronic liver failure; Acute-On-Chronic Liver Failure - etiology; Acute-On-Chronic Liver Failure - immunology; Acute-On-Chronic Liver Failure - metabolism; Adult; Biomarkers - blood; Biomarkers - metabolism; Case-Control Studies; caspase-1; Cytokines - blood; Cytokines - genetics; Cytokines - metabolism; disease progression; Female; flow cytometry; HBV; hepatitis B; Hepatitis B virus; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - metabolism; Humans; immunohistochemistry; Inflammasome; inflammasomes; Inflammasomes - blood; Inflammasomes - immunology; Inflammasomes - metabolism; inflammation; interleukin-18; liver; Liver - immunology; Liver - metabolism; liver failure; macrophages; Macrophages - immunology; Macrophages - metabolism; Male; Middle Aged; monocyte/macrophage; monocytes; Monocytes - immunology; Monocytes - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - blood; NLR Family, Pyrin Domain-Containing 3 Protein - immunology; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; patients; quantitative polymerase chain reaction; reverse transcriptase polymerase chain reaction; Western blotting; NLRP3; Inflammasome; Acute-on-Chronic liver failure; monocyte/macrophage; HBV
• ISSN: 0161-5890; 1872-9142; 1872-9142
• DOI: 10.1016/j.molimm.2020.01.011

•HBV-ACLF is a fatal consequence of HBV infection.•Little is known about the NLRP3 inflammasome and its related cytokines in ACLF population.•HBV-ACLF patients have lower expression of the NLRP3 inflammasome in peripheral CD14+ monocytes but higher expression in liver macrophages.•With disease progression different level of the NLRP3 inflammasome in periphery and liver reflect immune dysfunction of HBV-ACLF. The NLRP3 inflammasome has been suggested to play a crucial role in host antiviral defense, including against hepatitis B virus (HBV) infection. In the present study, we measured expression of NLRP3 and its related cytokines in patients with different stages of HBV-related acute-on-chronic liver failure (HBV-ACLF), a pattern of end-stage liver disease that occurs frequently in patients with chronic HBV (CHB) infection or HBV-related cirrhosis. A total of 75 subjects including 30 HBV-ACLF patients, 30 CHB patients, and 15 healthy controls (HCs) were enrolled. The NLRP3 inflammasome and its components (caspase-1, interleukin (IL)-1β, and IL-18) were measured in peripheral blood mononuclear cells (PBMCs), macrophages, and liver using flow cytometry, quantitative real-time polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry. The LPS was used to evaluate changes in NLRP3 and its related cytokines in CD14+ monocytes which may reflect immune status. Cytokine expression was measured using RT-PCR. Patients with HBV-ACLF had lower NLRP3 inflammasome expression in peripheral CD14+ monocytes, particularly in the middle-to-late stage, but higher expression in liver macrophages compared to CHB and HCs. Compared with H-LPS or L-LPS alone, L-LPS sequential H-LPS can significantly inhibit the expression of NLRP3 and its related cytokines. Differential expression patterns of the NLRP3 inflammasome in the periphery and liver might be related to immune dysfunction and recruitment of monocytes to the injured liver during disease progression. Persistent systemic inflammation is likely a cause of compromised immune status in patients with HBV-ACLF.