title: Distinct kinetics in the frequency of peripheral CD4+ T cells in patients with ulcerative colitis experiencing a flare during treatment with mesalazine or with a herbal preparation of myrrh, chamomile, and coffee charcoal.
abstract: BACKGROUND
  We found the first evidence of the efficacy of a herbal treatment with myrrh, dry extract of chamomile flowers, and coffee charcoal for ulcerative colitis (UC). However, the impact of the herbal treatment on the CD4+ T-cell compartment, which is essential for both the induction of UC and the maintenance of tolerance in the gut, is not well understood.
  
  
  OBJECTIVE
  To analyze the frequency and functional phenotype of CD4+ T cells and of immune-suppressive CD4+CD25high regulatory T cells (Tregs) in healthy control subjects, patients with UC in remission, and patients with clinical flare of UC.
  
  
  METHODS
  Patients in clinical remission were treated with either mesalazine or the herbal preparation for 12 months. The frequencies of whole CD4+ T cells, CD4+CD25med effector T cells, and Tregs and the expression of Foxp3 within the CD4+CD25hig Tregs were determined by flow cytometry at 6 time points. We determined the suppressive capability of Tregs from healthy control subjects and from patients in remission or clinical flare.
  
  
  RESULTS
  A total of 79 patients (42 women, 37 men; mean age, 48.5 years; 38 with clinical flare) and 5 healthy control subjects were included in the study. At baseline the frequencies of whole CD4+ T cells, CD4+CD25med effector cells, and Tregs did not differ between the two treatment groups and the healthy control subjects. In addition, patients with UC in sustained clinical remission showed no alteration from baseline after 1, 3, 6, 9, or 12 months of either treatment. In contrast, CD4+ T cells, CD4+CD25med effector T cells, and Tregs demonstrated distinctly different patterns at time points pre-flare and flare. The mesalazine group showed a continuous but not statistically significant increase from baseline to pre-flare and flare (p = ns). In the herbal treatment group, however, the percentage of the CD4+ T cells was lower at pre-flare than at baseline. This decrease was completely reversed after flare, when a significant increase was seen (CD4+CD25med pre-flare/flare p = 0.0461; CD4+CD25high baseline/flare p = 0.0269 and pre-flare/flare p = 0.0032). In contrast, no changes in the expression of Foxp3 cells were detected within the subsets of CD4+CD25high regulatory T cells. Of note, no alterations were detected in the suppressive capability of CD4+CD25high regulatory T cells isolated from the peripheral blood of healthy donors, from patients in remission, or from patients with clinical flare.
  
  
  CONCLUSIONS
  In patients with UC experiencing acute flare, the CD4+ T compartment demonstrates a distinctly different pattern during treatment with myrrh, chamomile extract, and coffee charcoal than during treatment with mesalazine. These findings suggest an active repopulation of regulatory T cells during active disease.
  
  
  BACKGROUND
  EU Clinical Trials Register 2007-007928-18/DE.
authors.affiliation: Department for Integrative Gastroenterology, Kliniken Essen-Mitte, University of Duisburg-Essen, Essen, Germany; Department for Internal and Integrative Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen, Essen, Germany.
authors.forename: Jost
authors.initials: J
authors.lastname: Langhorst
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Frede
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Knott
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Pastille
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.affiliation: Department for Internal and Integrative Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen, Essen, Germany.
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Dobos
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Westendorf
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D020843:Chamomile / Q000737:chemistry*; D002606:Charcoal / Q000627:therapeutic use*; D003069:Coffee; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use*; D008875:Middle Aged; D010936:Plant Extracts / Q000627:therapeutic use*; D013729:Terpenes / Q000737:chemistry*; D055815:Young Adult
chemical_list: D003069:Coffee; D010936:Plant Extracts; D013729:Terpenes; D002606:Charcoal; D019804:Mesalamine; C014119:myrrh oil