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Macrophage migration inhibitory factor expression correlates with inflammatory changes in human chronic hepatitis B infection

Authors

  • Hai-Ying Zhang,

    1. Departments of 1Medicine2Pathology, The University of Hong Kong, Hong Kong, SAR, China, 3Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA, 4Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China, 5Department of Medicine-Nephrology, Baylor College of Medicine, Houston, TX, USA.
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  • 1 Amin A. Nanji,

    1. Departments of 1Medicine2Pathology, The University of Hong Kong, Hong Kong, SAR, China, 3Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA, 4Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China, 5Department of Medicine-Nephrology, Baylor College of Medicine, Houston, TX, USA.
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  • 2,3 John M. Luk,

    1. Departments of 1Medicine2Pathology, The University of Hong Kong, Hong Kong, SAR, China, 3Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA, 4Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China, 5Department of Medicine-Nephrology, Baylor College of Medicine, Houston, TX, USA.
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  • 4 Xiao-Ru Huang,

    1. Departments of 1Medicine2Pathology, The University of Hong Kong, Hong Kong, SAR, China, 3Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA, 4Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China, 5Department of Medicine-Nephrology, Baylor College of Medicine, Houston, TX, USA.
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  • 1,5 Chung-Mau Lo,

    1. Departments of 1Medicine2Pathology, The University of Hong Kong, Hong Kong, SAR, China, 3Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA, 4Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China, 5Department of Medicine-Nephrology, Baylor College of Medicine, Houston, TX, USA.
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  • 4 Yong Xiong Chen,

    1. Departments of 1Medicine2Pathology, The University of Hong Kong, Hong Kong, SAR, China, 3Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA, 4Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China, 5Department of Medicine-Nephrology, Baylor College of Medicine, Houston, TX, USA.
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  • 1 Siu-Tsan Yuen,

    1. Departments of 1Medicine2Pathology, The University of Hong Kong, Hong Kong, SAR, China, 3Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA, 4Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China, 5Department of Medicine-Nephrology, Baylor College of Medicine, Houston, TX, USA.
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  • 2 Hui Y. Lan,

    1. Departments of 1Medicine2Pathology, The University of Hong Kong, Hong Kong, SAR, China, 3Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA, 4Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China, 5Department of Medicine-Nephrology, Baylor College of Medicine, Houston, TX, USA.
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  • and 1,5 George K. K. Lau 1

    1. Departments of 1Medicine2Pathology, The University of Hong Kong, Hong Kong, SAR, China, 3Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA, 4Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China, 5Department of Medicine-Nephrology, Baylor College of Medicine, Houston, TX, USA.
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Dr. George K. K. Lau, University Department of Medicine, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, SAR, China.
Tel: +852 28553578
Fax: +852 28190694
e-mail: gkklau@netvigator.com

Abstract

Background: Macrophage migration inhibitory factor (MIF) has emerged to be a pivotal cytokine in immune-mediated diseases.

Patients and methods: To investigate the role of MIF in chronic hepatitis B infection, we studied two groups of hepatitis B surface antigen positive patients: group 1 (immune tolerant, n=16) and group 2 (immune clearance, n=16). Serum level of MIF was measured by enzyme-linked immunosorbent assay and intrahepatic expression of MIF, macrophage and T-cell localisation were detected by double immunohistochemistry.

Results: An increased serum MIF correlated significantly with increased serum alanine aminotransferase activity (r=0.73, P<0.001) and the severity of necroinflammatory injury (r=0.642, P<0.001). In group 2, there was marked MIF mRNA expression in all KP-1+ macrophages and CD45RO+ activated T cells and, to a lesser extent, in hepatocytes within inflammatory areas. In contrast to its mRNA expression, the cytoplasmic MIF protein level in hepatocytes, infiltrating macrophages and T cells within the inflammatory area was reduced, which probably contributed to the increased serum MIF level.

Conclusions: Our data suggested that MIF played a role in sustaining cell-mediated hepatic injury during the immune-clearance phase of chronic hepatitis B infection.

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