DAMP molecular IL-33 augments monocytic inflammatory storm in hepatitis B-precipitated acute-on-chronic liver failure.

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. 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. 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. DAMP molecular IL-33 augmented the 'storm' of monocytic inflammation in response to LPS through ERK1/2 activation during HB-ACLF.