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

摘要

Abstract 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/ ST 2 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 CD 80 expression, phagocytosis capacity, cytokine secretion and MAP kinase activation induced by LPS were detected to explore the role of IL ‐33/ ST 2 signal in regulating monocyte function in patients. Results The expression levels of IL ‐33/ ST 2 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 , CCR 2 and CD 80 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 ERK 1/2 activation of monocytes in response to LPS . Conclusions DAMP molecular IL ‐33 augmented the ‘storm’ of monocytic inflammation in response to LPS through ERK 1/2 activation during HB ‐ ACLF .