Background and aims: The intestinal microbiota play a pivotal role in the inflammation associated with Crohn’s disease through their interaction with the mucosal immune system. Some bifidobacteria species are immunor...
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Background and aims: The intestinal microbiota play a pivotal role in the inflammation associated with Crohn’s disease through their interaction with the mucosal immune system. Some bifidobacteria species are immunoregulatory and induce increased dendritic cell interleukin 10 (IL- 10) release in vitro. Fructo-oligosaccharides (FOS) increase faecal and mucosal bifidobacteria in healthy volunteers. The aim of this study was to assess the effect of FOS administration on disease activity, bifidobacteria concentrations, and mucosal dendritic cell function in patients with moderately active Crohn’s disease. Patients and methods: Ten patients with active ileocolonic Crohn’s disease received 15 g of FOS for three weeks. Disease activity was measured using the Harvey Bradshaw index. Faecal and mucosal bifidobacteria were quantified by fluorescence in situ hybridisation, and mucosal dendritic cell IL- 10 and Toll-like receptor (TLR) expression were assessed by flow cytometry of dissociated rectal biopsies. Results: FOS induced a significant reduction in the Harvey Bradshaw index from 9.8 (SD 3.1) to 0.9 (3.4) (p < 0.01). There was a significant increase in faecal bifidobacteria concentration from 8.8 (0.9) log10 to 9.4 (0.9)- log10 cells/g dry faeces (p < 0.001). The percentage of IL- 10 positive dendritic cells increased from 30 (12)% to 53 (10)% (p = 0.06). Finally, the percentage of dendritic cells expressing TLR2 and TLR4 increased from 1.7 (1.7)% to 36.8 (15.9)% (p = 0.08) and from 3.6 (3.6)% to 75.4 (3.4)% (p < 0.001), respectively. Conclusions: FOS supplementation increases faecal bifidobacteria concentrations and modifies mucosal dendritic cell function. This novel therapeutic strategy appears to decrease Crohn’s disease activity in a small open label trial and therefore warrants further investigation.
Background/Aims: Hepatitis C virus (HCV) causes a chronic infection that can lead to fibrosis and carcinoma. Immune responses mediated by cytotoxic T lymphocytes (CTLs) could be involved in viral clearance or persiste...
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Background/Aims: Hepatitis C virus (HCV) causes a chronic infection that can lead to fibrosis and carcinoma. Immune responses mediated by cytotoxic T lymphocytes (CTLs) could be involved in viral clearance or persistence, and therefore in determining the course of the disease. Methods: Intrahepatic and peripheral blood CD8+ T cells were obtained from 32 HCV-chronically infected patients and analysed by flow-cytometry for surface markers of differentiation, IFNγ and TNFα production, degranulation capacity and perforin content, after CD3 triggering. Results were compared with those obtained from 13 patients with a non-viral liver disease. Results: Intrahepatic CD8+ T cells of HCV-infected patiets, despite their phenotype of pre-terminally and terminally differentiated effectors (CCR7- CD45RA- /+ ), are poorly responsive to T cell receptor (TCR)mediated stimulation compared with those obtained from uninfected subjects. This defect correlates with the severity of fibrosis, is more pronounced in patients with ALT< 1.5× N than with ALT >1.5× N U/ml, and is not evident after mitogen stimulation. Conclusions: The present study describes the accumulation of hypo-responsive CD8+ T cells in the liver of patients with chronic HCV infection. Understanding the mechanisms underlying this impairment may be helpful in the design of innovative strategies for HCV treatment.
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