title: Bilberry-Derived Anthocyanins Modulate Cytokine Expression in the Intestine of Patients with Ulcerative Colitis.
abstract: We previously demonstrated that anthocyanin-rich bilberry extract (ARBE) inhibits IFN-γ-induced signalling and downstream effects in human monocytic cells and ameliorates disease activity in ulcerative colitis (UC) patients. Here, we studied the molecular mechanisms of ARBE-mediated effects in vitro and by analysing colonic tissue and serum samples of UC patients treated with an oral anthocyanin-rich bilberry preparation during an open label clinical trial.
  
  
  
  Colon specimens obtained during an open pilot study using ARBE for the treatment of mild-to-moderate UC were analyzed by immunohistochemistry. Cytokine levels in patients' serum were quantified by ELISA. Cell culture experiments were performed using THP-1 monocytic cells.
  
  
  
  ARBE treatment inhibited the expression of IFN-γ-receptor 2 in human THP-1 monocytic cells. Colon biopsies of UC patients who responded to the 6-week long ARBE treatment revealed reduced amounts of the pro-inflammatory cytokines IFN-γ and TNF-α. Levels of phosphorylated (activated) p65-NF-κB were reduced in these patients. Further, patients with successful ARBE treatment featured enhanced levels of Th17-cell specific cytokine IL-22 and immunoregulatory cytokine IL-10 as well as reduced serum levels of TNF-α and MCP-1, but enhanced levels of IL-17A, in contrast to patients that did not reach remission after ARBE treatment.
  
  
  
  Our data suggest a molecular mechanism underlying the anti-inflammatory effects of ARBE treatment in UC patients by modulating T-cell cytokine signalling and inhibiting IFN-γ signal transduction. These data are of particular interest, since ARBE is a promising therapeutic approach for the treatment of IBD.
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Sofia
authors.initials: S
authors.lastname: Roth
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Marianne R
authors.initials: MR
authors.lastname: Spalinger
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gottier
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Luc
authors.initials: L
authors.lastname: Biedermann
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Zeitz
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lang
authors.affiliation: Institute for Surgical Pathology, University Hospital Zürich, Zurich, Switzerland.
authors.forename: Achim
authors.initials: A
authors.lastname: Weber
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.|Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.|Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Scharl
mesh_terms: D000328:Adult; D000872:Anthocyanins / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D029800:Vaccinium myrtillus / Q000737:chemistry*
chemical_list: D000872:Anthocyanins; D016207:Cytokines