A novel role for adiponectin in regulating the immune responses in chronic hepatitis C virus infection
Open Access
- 21 April 2008
- journal article
- viral hepatitis
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 48 (2), 374-384
- https://doi.org/10.1002/hep.22387
Abstract
Adipose tissue releases pro-inflammatory and anti-inflammatory mediators, including adiponectin, which elicit a broad range of metabolic and immunological effects. The study aim was to determine in subjects infected with chronic hepatitis C virus (HCV) the effects of total adiponectin and its high-molecular-weight (HMW) and low-molecular-weight isoforms on HCV-specific immune responses. Serum levels of total adiponectin and its isoforms were determined by immunoassay. The ex vivo effect of adiponectin on the HCV-specific T-cell response was examined by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot and enzyme-linked immunosorbent assay cytokine assays. The role of the mitogen-activated protein kinase (MAPK) signaling pathway in mediating the adiponectin effect on T cells was also evaluated. We found that serum levels of total and HMW adiponectin were significantly decreased in subjects with chronic HCV and increased body mass index (BMI) compared with HCV-infected lean subjects. The presence of an anti-HCV specific immune response was strongly associated with lower BMI (P = 0.004) and higher serum total (P = 0.01) and HMW (P = 0.02) adiponectin. In ex vivo assays, total adiponectin and the HMW adiponectin isoform enhanced HCV-specific IFN-γ production (P = 0.02 and 0.03, respectively). Adiponectin-R1 receptors were expressed on T cells and monocytes. In depletion experiments, the IFN-γ response to adiponectin was entirely dependent on the simultaneous presence of both CD4 and CD8 T cells, and to a lesser extent, natural killer cells. Selective inhibition of p38MAPK activity by SB203580 abrogated the IFN-γ response to adiponectin, whereas extracellular signal-regulated kinase 1/2 inhibition by PD98059 did not affect the response. Conclusion: In chronic HCV, a reciprocal association exists between BMI, adiponectin, and the anti-HCV immune responses, emphasizing the important role played by adiposity in regulating the immune response in HCV infection. (HEPATOLOGY 2008;48:374–384.)Keywords
This publication has 45 references indexed in Scilit:
- Selective purification and characterization of adiponectin multimer species from human plasmaBiochemical and Biophysical Research Communications, 2007
- Adiponectin Increases Fatty Acid Oxidation in Skeletal Muscle Cells by Sequential Activation of AMP-Activated Protein Kinase, p38 Mitogen-Activated Protein Kinase, and Peroxisome Proliferator–Activated Receptor αDiabetes, 2006
- Protective immunity against hepatitis C virus infectionImmunology & Cell Biology, 2006
- Relationship Between Steatosis, Inflammation, and Fibrosis in Chronic Hepatitis C: A Meta-Analysis of Individual Patient DataGastroenterology, 2006
- Different effects of adiponectin isoforms in human monocytic cellsJournal of Leukocyte Biology, 2006
- Insulin resistance and steatosis in hepatitis C virus infectionGut, 2005
- The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patientsJournal of Hepatology, 2004
- Viral and immunological determinants of hepatitis C virus clearance, persistence, and diseaseProceedings of the National Academy of Sciences, 2002
- Genomic analysis of the host response to hepatitis C virus infectionProceedings of the National Academy of Sciences, 2002
- Interleukin 10 treatment reduces fibrosis in patients with chronic hepatitis C: A pilot trial of interferon nonrespondersGastroenterology, 2000