Introduction Neutrophil dysfunction has been reported in patients with alcohol-related cirrhosis (ARC) and is associated with increased risk of infection and mortality. There is a paucity of understanding regarding the mechanisms of immune dysfunction in patients with active alcohol consumption and ARC. This study aimed to characterise neutrophil phenotype, functionality and plasma cytokine profiles in abstinent patients with ARC (n=17) compared to those actively drinking (n=19), split by MELD score <15 vs >15 compared to healthy controls (n=12).
Methods Neutrophils were isolated from patients with ARC. Phagocytic capacity was analysed by flow cytometry using FITC-labelled Escherichia coli and oxidative burst (OB) was determined by the percentage of neutrophils producing reactive oxygen species (ROS) at rest, and after stimulation with opsonised E Coli. Neutrophils were stained with anti-CD11b (APC-Cy7), -CD16 (PE) and –TLR4 (biotin-conjugated PE-Cy7 Streptavidin). Plasma cytokine profiling was performed using cytokine bead array.
Results Phagocytosis was significantly reduced in the cirrhotic groups compared to controls (p=0.02) however this was not influenced by MELD score or abstinence. Spontaneous OB was significantly increased in the cirrhotic groups compared to controls (p=0.03). Median spontaneous OB in the abstinent patients with MELD <15 was 26% [IQR 8–42] compared to 10% (IQR 7–44) in those actively drinking. Median spontaneous OB in the abstinent group with MELD>15 was 31% (IQR 8–61) compared to 14% (IQR 4–29) in the active alcohol-drinkers. Stimulated burst was not impaired in the cirrhotic groups, with comparative values to controls. Plasma pro- and anti-inflammatory cytokine profiles were not discriminatory between the groups. Baseline TLR4 expression was increased in the MELD>15 abstinent group compared to active drinkers (p=0.004); alcohol attenuated resting TLR4 expression to values seen in controls.
Conclusion Active alcohol consumption did not impact on neutrophil phagocytic capacity but reduced spontaneous OB by 50% with a reduction in the generation of ROS and decreased resting TLR4 expression. This supports a paradoxical anti-oxidant role of active alcohol drinking in patients with ARC that may promote endotoxin tolerance and warrants further investigation.
Competing interests None declared.
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