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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
Author(s) -
Khanam Arshi,
Trehanpati Nirupama,
Garg Vishal,
Kumar Chandan,
Garg Hitendra,
Sharma Barjesh C.,
Sarin Shiv K.
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12415
Subject(s) - granulocyte colony stimulating factor , cd8 , flow cytometry , immune system , medicine , immunology , granulocyte , stimulation , endocrinology , chemotherapy
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 CD 34 + 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 ( mDC s) and plasmacytoid ( pDC s) 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‐γ production was compared in both groups following stimulation of PBMCs with phorbol myristate acetate (PMA). Results In Group A , circulating and intrahepatic mDC s, pDC s ( 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‐γ‐producing CD8 T cells were significantly decreased ( P > 0.05) along with decreased serum bilirubin and international normalized ratio (INR). Intrahepatic DCs and IFN‐γ level were compared in survivor and non‐survivor. Non‐survivors from both groups, showed decreased DCs, high IFN‐γ 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 ‐γ secreting CD 8 T cells with improved clinical severity indices. Decreased IFN ‐ γ 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.