Interleukin-33 Promotes Disease Progression in Patients with Primary Biliary Cirrhosis

Interleukin-33 Promotes Disease Progression in Patients with Primary Biliary Cirrhosis

YONGQIANG SUN,^1,2 JI-YUAN ZHANG,³ SA LV,³ HUAN WANG,⁴ MAN GONG,² NING DU,² HONGHONG LIU,² NING ZHANG,² JING JING,² CHAO ZHOU,² FAN ZHANG² and ZONGREN WANG¹

¹Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi Province, P.R. China
²Integrative Medical Center Liver Diseases, Beijing 302 Hospital, Beijing, P.R. China
³Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, P.R. China
⁴Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi Province, P.R. China

Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease that can cause a series of complications, including cirrhosis, liver failure and hepatocellular carcinoma. Interleukin-33 (IL-33) is expressed in various non-hematopoietic cells and a certain population of immune cells, and exerts its biological effects by binding to the specific receptor, suppression of tumorigenicity 2 (ST2). A soluble form of ST2 (sST2) has been postulated to act as a decoy receptor for IL-33. In this study, we aimed to investigate the role of IL-33 in the pathogenesis of PBC. The study included 20 healthy controls and 68 patients with PBC. We thus found the increased serum IL-33 levels in PBC patients. Its elevated levels were positively correlated with serum alkaline phosphatase levels (a key parameter for the definition of PBC) and with Child-Pugh scores, which were used to determine the prognosis of liver cirrhosis. Moreover, the serum concentrations of sST2 were significantly higher in PBC patients compared with healthy subjects, irrespective of the disease severity. Importantly, the cells that express IL-33 and/or myeloperoxidase (a marker for neutrophils) were accumulated in the livers of PBC patients, and their number increased with the severity of liver lesions. Lastly, in vitro chemotaxis assays revealed that IL-33 enhanced the migration of neutrophils. These data suggest that IL-33 may affect the progress of PBC by recruiting neutrophils to the liver. This expanded knowledge of IL-33 in PBC patients is important for developing therapeutic strategies (e.g., neutralization of IL-33), selecting optimal clinical management, and predicting prognosis.

keywords —— disease progression; immune pathogenesis; interleukin-33; liver lesion; primary biliary cirrhosis

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Tohoku J. Exp. Med., 2014, 234, 255-261

Correspondence: Zongren Wang, Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi Province 710032, P.R. China.

e-mail: yanfengyun2011@126.com