Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NAPDH oxidase
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Authors
Vergis, Nikhil
Khamri, Wafa
Beale, Kylie
Sadiq, Fouzia
Aletrari, Mina O
Moore, Celia
Atkinson, Stephen R
Bernsmeier, Christine
Possamai, Lucia A
Petts, Gemma
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Issue Date
2017
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Article
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Abstract
OBJECTIVE: In order to explain the increased susceptibility to serious infection in alcoholic hepatitis, we evaluated monocyte phagocytosis, aberrations of associated signalling pathways and their reversibility, and whether phagocytic defects could predict subsequent infection. DESIGN: Monocytes were identified from blood samples of 42 patients with severe alcoholic hepatitis using monoclonal antibody to CD14. Phagocytosis and monocyte oxidative burst (MOB) were measured ex vivo using flow cytometry, luminometry and bacterial killing assays. Defects were related to the subsequent development of infection. Intracellular signalling pathways were investigated using western blotting and PCR. Interferon-γ (IFN-γ) was evaluated for its therapeutic potential in reversing phagocytic defects. Paired longitudinal samples were used to evaluate the effect of in vivo prednisolone therapy. RESULTS: MOB, production of superoxide and bacterial killing in response to CONCLUSIONS: Monocyte oxidative burst and bacterial killing is impaired in alcoholic hepatitis while bacterial uptake by phagocytosis is preserved. Defective MOB is associated with reduced expression of NADPH oxidase in these patients and predicts the development of infection and death.
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Journal
Gut
Volume
66
Issue
3