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.
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.
Authors: Bruno Costa-Silva; Nicole M Aiello; Allyson J Ocean; Swarnima Singh; Haiying Zhang; Basant Kumar Thakur; Annette Becker; Ayuko Hoshino; Milica Tešić Mark; Henrik Molina; Jenny Xiang; Tuo Zhang; Till-Martin Theilen; Guillermo García-Santos; Caitlin Williams; Yonathan Ararso; Yujie Huang; Gonçalo Rodrigues; Tang-Long Shen; Knut Jørgen Labori; Inger Marie Bowitz Lothe; Elin H Kure; Jonathan Hernandez; Alexandre Doussot; Saya H Ebbesen; Paul M Grandgenett; Michael A Hollingsworth; Maneesh Jain; Kavita Mallya; Surinder K Batra; William R Jarnagin; Robert E Schwartz; Irina Matei; Héctor Peinado; Ben Z Stanger; Jacqueline Bromberg; David Lyden Journal: Nat Cell Biol Date: 2015-05-18 Impact factor: 28.824
Authors: David N Assis; Lin Leng; Xin Du; Clarence K Zhang; Gerrit Grieb; Melanie Merk; Alvaro Baeza Garcia; Catherine McCrann; Julius Chapiro; Andreas Meinhardt; Yuka Mizue; David J Nikolic-Paterson; Jürgen Bernhagen; Marshall M Kaplan; Hongyu Zhao; James L Boyer; Richard Bucala Journal: Hepatology Date: 2013-12-20 Impact factor: 17.425
Authors: Mark A Barnes; Megan R McMullen; Sanjoy Roychowdhury; Sorana G Pisano; Xiuli Liu; Abram B Stavitsky; Richard Bucala; Laura E Nagy Journal: Hepatology Date: 2013-01-18 Impact factor: 17.425