In Crohn's Disease, Anti-TNF-α Treatment Changes the Balance between Mucosal IL-17, FOXP3, and CD4 Cells.

Abstract

Aim. In Crohn's disease (CD), anti-TNF-α treatment is a potent medication. We aimed to characterize the effect of anti-TNF-α treatment on T effector and regulatory cells. Material and Methods. We studied T-effector and regulatory cells on cellular and mRNA levels in intestinal biopsy samples from 13 Crohn's disease patient. Biopsies were obtained at baseline and 3 months after anti-TNF-α treatment, and from 14 inflammation-free control subjects. Results. Patients had higher numbers of ileal IL-17(+) and forkhead box P3 (FOXP3)(+) cells than did control subjects, both before ( P ≤ 0.001 and P ≤ 0.05, resp.) and after the anti-TNF-α treatment (P ≤ 0.01, P ≤ 0.01). Intestinal interferon-γ and IL-17 mRNA expression was higher in Crohn's disease and remained elevated after anti-TNF-α treatment. The ratio of IL-17(+) cells to CD4(+) cells decreased (P ≤ 0.05) and compared to baseline the ratio of IL-17(+) cells to FOXP3(+) was lower after treatment (P ≤ 0.05). Conclusions. TNF-α-blocking agents improved intestinal balance between IL-17(+) T-effector and regulatory T cells, although intestinal IL-17 upregulation remained elevated.