Journal of Hepatology
Volume 48, Issue 6 , Pages 945-951, June 2008

Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis

Liver Failure Group, The Institute of Hepatology, Division of Medicine, University College London, 69-75 Chenies Mews, London WC1E 6HX, UK

Received 13 December 2007; received in revised form 28 January 2008; accepted 24 February 2008. published online 25 March 2008.

Associate Editor: C.P. Day

Background/Aim

Endotoxaemia contributes to neutrophil dysfunction, infection risk and mortality in patients with alcoholic cirrhosis. As probiotics may decrease Gram-negative gut organisms, we hypothesised that probiotic treatment would restore neutrophil function.

Methods

In an open-label study, patients with alcoholic cirrhosis (n=12) received Lactobacillus casei Shirota (6.5×109) 3 times daily for 4 weeks. Data were compared to healthy controls (n=13) and cirrhotic patients (n=8) who did not receive probiotics. Neutrophil oxidative burst, phagocytosis, toll-like-receptor (TLR) expression, plasma cytokines and ex vivo endotoxin-stimulated cytokine production were measured.

Results

Baseline neutrophil phagocytic capacity in patients was significantly lower compared to healthy controls (73% versus 98%, p<0.05), but normalised at the end of the study (n=10, 100%, p<0.05). No improvement was seen in disease controls. Soluble TNF-receptor (sTNFR)-1 and-2 and interleukin (IL)10 were significantly elevated in patients’ plasma but did not change during the study. Ex vivo endotoxin-stimulated levels of sTNFR1, sTNFR2 and IL10 were significantly lower at the end of the study (p<0.05). TLR2, 4 and 9 were overexpressed in patients. TLR4 expression normalised by the end of the study.

Conclusions

Our data provide a proof-of-concept that probiotics restore neutrophil phagocytic capacity in cirrhosis, possibly by changing IL10 secretion and TLR4 expression, warranting larger randomised controlled and mechanistic studies.

Abbreviations: TNFα, tumour necrosis factor alpha, sTNFR, soluble tumour necrosis factor alpha receptor, TLR, Toll-like receptor, IL, interleukin

Keywords: Alcoholic cirrhosis, Neutrophil function, Phagocytosis, Probiotic, Cytokine, Toll-like receptor

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 31.50 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

 The authors who have taken part in the research of this paper declared that they received funding from the manufacturers to carry out their research.

PII: S0168-8278(08)00195-5

doi:10.1016/j.jhep.2008.02.015

Journal of Hepatology
Volume 48, Issue 6 , Pages 945-951, June 2008