title: A novel role for adiponectin in regulating the immune responses in chronic hepatitis C virus infection.
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-gamma) 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-gamma production (P = 0.02 and 0.03, respectively). Adiponectin-R1 receptors were expressed on T cells and monocytes. In depletion experiments, the IFN-gamma 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-gamma response to adiponectin, whereas extracellular signal-regulated kinase 1/2 inhibition by PD98059 did not affect the response.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Clovis
authors.initials: C
authors.lastname: Palmer
authors.forename: Taline
authors.initials: T
authors.lastname: Hampartzoumian
authors.forename: Andrew
authors.initials: A
authors.lastname: Lloyd
authors.forename: Amany
authors.initials: A
authors.lastname: Zekry
mesh_terms: D052242:Adiponectin / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology; D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D018937:Hepatitis C Antibodies / Q000096:biosynthesis*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural; D007962:Leukocytes / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C475418:ADIPOR1 protein, human; D052242:Adiponectin; D016207:Cytokines; D018937:Hepatitis C Antibodies; D054419:Receptors, Adiponectin; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases