title: Altered frequencies of dendritic cells and IFN-gamma-secreting T cells with granulocyte colony-stimulating factor (G-CSF) therapy in acute-on- chronic liver failure.
abstract: OBJECTIVE
  Acute-on-chronic liver failure (ACLF) is a serious hepatic ailment with impaired immunity and poor treatment options resulting high mortality. Treatment with granulocyte colony-stimulating factor(G-CSF) mobilizes CD34(+) cells in ACLF patients; however its effect on impaired immune responses remains to be elucidated. To analyse the effect of G-CSF in immune modulation in ACLF.
  
  
  METHODS
  We have analysed the frequencies of circulating and intrahepatic myeloid (mDCs) and plasmacytoid(pDCs) dendritic cells (DCs) and T cells in ACLF patients treated with G-CSF (Group A; n = 23) and placebo (Group B; n = 24) using flow cytometry. IFN-c production was compared in both groups following stimulation of PBMCs with phorbol myristate acetate (PMA).
  
  
  RESULTS
  In Group A, circulating and intrahepatic mDCs, pDCs (P < 0.04, P < 0.02) and T cells(CD3, CD4 and CD8) increased significantly post-G-CSF treatment in comparison to placebo group. Importantly in Group A, IFN-c-producing CD8 T cells were significantly decreased (P > 0.05) along with decreased serum bilirubin and international normalized ratio (INR). Intrahepatic DCs and IFN-clevel were compared in survivor and non-survivor. Non-survivors from both groups, showed decreased DCs, high IFN-c level and no improvement in clinical parameters including s-bilirubin and INR.
  
  
  CONCLUSIONS
  G-CSF therapy increased the frequencies of dendritic cells and reduced IFN-c secreting CD8 T cells with improved clinical severity indices. Decreased IFN- c production may contribute to reduced hepatocellular damage in ACLF patients.Our observations support the basis for further use of G-CSF therapy as immune modulator in these patients.
authors.forename: Arshi
authors.initials: A
authors.lastname: Khanam
authors.forename: Nirupama
authors.initials: N
authors.lastname: Trehanpati
authors.forename: Vishal
authors.initials: V
authors.lastname: Garg
authors.forename: Chandan
authors.initials: C
authors.lastname: Kumar
authors.forename: Hitendra
authors.initials: H
authors.lastname: Garg
authors.forename: Barjesh C
authors.initials: BC
authors.lastname: Sharma
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Sarin
mesh_terms: D000328:Adult; D002452:Cell Count; D015331:Cohort Studies; D003713:Dendritic Cells / Q000276:immunology*; D058625:End Stage Liver Disease / Q000150:complications*; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate