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

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. AIM: To analyze the frequency and functional phenotype of CD4(+) T cells and of immune-suppressive CD4+CD25(high) 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(+)CD25(med) effector T cells, and Tregs and the expression of Foxp3 within the CD4(+)CD25(hig) 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(+)CD25(med) 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(+)CD25(med)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(+)CD25(med) pre-flare/flare p = 0.0461; CD4(+)CD25(high) 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(+)CD25(high) regulatory T cells. Of note, no alterations were detected in the suppressive capability of CD4(+)CD25(high) 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. TRIAL REGISTRATION: EU Clinical Trials Register 2007-007928-18/DE