DAMP molecular IL-33 augments monocytic inflammatory storm in hepatitis B-precipitated acute-on-chronic liver failure.
BACKGROUND & AIMS
Patients with acute-on-chronic liver failure (ACLF) usually exhibit defective monocyte function and excessive systemic inflammatory response. Interleukin-33 (IL-33) acts as a danger-associated molecular pattern (DAMP) to modulate immune response. However, the role of IL-33 in regulating monocyte function during hepatitis B-precipitated ACLF (HB-ACLF) in response to lipopolysaccharide (LPS) has not been clear.


METHODS
In this study, the levels of IL-33/ST2 in blood and liver samples collected from patients with HB-ACLF, chronic hepatitis B (CHB) and normal controls and the associated of those findings with disease severity were analysed. HLA-DR and CD80 expression, phagocytosis capacity, cytokine secretion and MAP kinase activation induced by LPS were detected to explore the role of IL-33/ST2 signal in regulating monocyte function in patients.


RESULTS
The expression levels of IL-33/ST2 were significantly increased in peripheral blood and livers of patients with HB-ACLF, as compared with patients with CHB and controls. It was found that serum IL-33 level was associated with severity of liver disease. Treatment with IL-33 on monocytes significantly increased HLA-DR, CCR2 and CD80 expression, enhanced LPS-stimulated TNF-α, IL-6 and IL-1β secretion, but did not affect the phagocytic capacity. Furthermore, IL-33 signalling enhanced the ERK1/2 activation of monocytes in response to LPS.


CONCLUSIONS
DAMP molecular IL-33 augmented the 'storm' of monocytic inflammation in response to LPS through ERK1/2 activation during HB-ACLF.
['Du|Xing X|XX|', 'Shi|Yu|Y|0000-0002-9392-7176', 'Yang|Ying|Y|', 'Yu|Ye|Y|', 'Lou|Hua G|HG|', 'Lv|Fang F|FF|', 'Chen|Zhi|Z|', 'Yang|Qiao|Q|0000-0001-7401-2168']
D065290:Acute-On-Chronic Liver Failure D000328:Adult D016022:Case-Control Studies D002478:Cells, Cultured D004789:Enzyme Activation D048049:Extracellular Signal-Regulated MAP Kinases D005260:Female D006684:HLA-DR Antigens D006515:Hepatitis B virus D019694:Hepatitis B, Chronic D054884:Host-Pathogen Interactions D006801:Humans D018836:Inflammation Mediators D000072179:Interleukin-1 Receptor-Like 1 Protein D000067596:Interleukin-33 D008070:Lipopolysaccharides D008297:Male D008875:Middle Aged D009000:Monocytes D010587:Phagocytosis D012720:Severity of Illness Index D015398:Signal Transduction D055815:Young Adult
monocyte acute-on-chronic liver failure Interleukin-33 immune regulation