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INFLAMMATORY BOWEL DISEASE |
production in Crohns disease can be downregulated ex vivo by probiotic bacteria
1 Digestive System Research Unit, Hospitals Vall dHebron, Autonomous University, Barcelona, Spain
2 Department of Surgery, Hospitals Vall dHebron, Autonomous University, Barcelona, Spain
Correspondence to:
Correspondence to:
Dr F Guarner, Digestive System Research Unit, Hospital General Vall dHebron, Barcelona 08035, Spain;
fguarnera{at}medynet.com
Background and aims: Tumour necrosis factor
(TNF-
) plays a key role in the pathogenesis of intestinal inflammation in Crohns disease. The effect of bacteria on TNF-
release by intestinal mucosa was investigated.
Methods: Ileal specimens were obtained at surgery from 10 patients with Crohns disease (ileal stricture) and five disease controls undergoing right hemicolectomy (caecal cancer). Mucosal explants from each specimen were cultured for 24 hours with either non-pathogenic Escherichia coli, Lactobacillus casei DN-114001, L bulgaricus LB10, or L crispatus (each study contained blank wells with no bacteria). Tissue and bacterial viability was confirmed by lactate dehydrogenase (LDH) release and culture. Concentrations of TNF-
were measured in supernatants and the phenotype of the intestinal lymphocytes was analysed by flow cytometry.
Results: Coculture of mucosa with bacteria did not modify LDH release. Release of TNF-
by inflamed Crohns disease mucosa was significantly reduced by coculture with L casei or L bulgaricus; changes induced by L crispatus or E coli were not significant. The effect of L casei and L bulgaricus was not prevented by protease inhibitors. Coculture with L casei and L bulgaricus reduced the number of CD4 cells as well as TNF-
expression among intraepithelial lymphocytes from Crohns disease mucosa. None of the bacteria induced changes in non-inflamed mucosa.
Conclusions: Probiotics interact with immunocompetent cells using the mucosal interface and modulate locally the production of proinflammatory cytokines.
Keywords: cytokines; inflammatory bowel disease; lymphocytes; microflora
Abbreviations: CFU, colony forming units; IEL, intraepithelial lymphocytes; IL, interleukin; LDH, lactate dehydrogenase; LPL, lamina propria lymphocytes; LB broth, Luria Bertani broth; MRS broth, Man-Rogosa-Sharpe broth; TNF-
, tumour necrosis factor 
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