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

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.