Altered Frequencies of Dendritic Cells and IFN-γ-secreting T Cells with Granulocyte Colony-Stimulating Factor (G-CSF) Therapy in Acute-on-Chronic Liver Failure

Background & Aims 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-gamma 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-gamma-producing CD8 T cells were significantly decreased (P>0.05) along with decreased serum bilirubin and international normalized ratio (INR). Intrahepatic DCs and IFN-gamma level were compared in survivor and non-survivor. Non-survivors from both groups, showed decreased DCs, high IFN-gamma 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-gamma secreting CD8 T cells with improved clinical severity indices. Decreased IFN- gamma 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.