Probiotic therapy in the prevention of pouchitis onset: decreased interleukin-1beta, interleukin-8, and interferon-gamma gene expression.
BACKGROUND
Probiotic therapy has been shown to prevent the onset of pouchitis and to improve the quality of life in ulcerative colitis patients who required ileal pouch anal anastomosis. Pouchitis has been associated with elevated levels of proinflammatory cytokines and chemokines.


METHODS
In this retrospective analysis of archived endoscopic samples from responding patients enrolled in the above-mentioned trial, we were interested in studying mucosal gene expression of the pleiotropic proinflammatory cytokines (interleukin-1beta, interleukin-6), TH1 cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-12), regulatory cytokines (interleukin-10, transforming growth factor-beta), and the chemokine interleukin-8. In addition to assessment of cytokine gene expression, the presence of polymorphonuclear cells in the mucosal tissue was evaluated.


RESULTS
Data show that patients who were treated with probiotics had significant lower mucosal mRNA expression levels of interleukin-1beta, interleukin-8, and interferon-gamma compared with placebo-treated patients. In addition, a lower number of polymorphonuclear cells was present in the tissue of patients within the probiotic group compared with the number of polymorphonuclear cells in the tissue of patients receiving placebo and patients having an episode of pouchitis.


CONCLUSIONS
These data suggest that probiotic treatment regulates the mucosal immune response by reducing mucosal levels of neutrophil-chemoattractant IL-8 and tissue influx of polymorphonuclear cells, and may further act by inhibition of T-cell activation, by reinforcement of barrier function and by a tight control of the potent pro-inflammatory cytokine IL-1beta.
Lammers
Karen M
KM
Policlinico S. Orsola, Department of Internal Medicine and Gastroenterology, University of Bologna, Italy. kmlammers@hotmail.com
Vergopoulos
Athanasios
A
Babel
Nina
N
Gionchetti
Paolo
P
Rizzello
Fernando
F
Morselli
Claudia
C
Caramelli
Elisabetta
E
Fiorentino
Michelangelo
M
d'Errico
Antonia
A
Volk
Hans-Dieter
HD
Campieri
Massimo
M
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009504:Neutrophils; D019449:Pouchitis / Q000378:metabolism* / Q000473:pathology; D019936:Probiotics / Q000494:pharmacology*; D012333:RNA, Messenger; D012189:Retrospective Studies
D015703:Antigens, CD; D000943:Antigens, Differentiation; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D008565:Membrane Proteins; D012333:RNA, Messenger; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1