Infliximab therapy decreases the levels of TNF-α and IFN-γ mRNA in colonic mucosa of ulcerative colitis

Abstract

Objective. The mechanisms of action of infliximab (IFX) in the treatment of ulcerative colitis (UC) are poorly understood. The aim of the study was to investigate the changes in tissue expression of tumor necrosis factor-alpha (TNF-α) and other cytokines in UC patients receiving IFX treatment. Material and methods. The levels of TNF-α, interleukin (IL)-10, IL-4, and interferon-gamma (IFN-γ) mRNA in colonic biopsies from 32 UC patients during IFX treatment were measured by real-time polymerase chain reaction (PCR) and compared with those of 19 controls. Immunohistochemistry was performed to characterize the changes of inflammatory cells during treatment. Results. IFX reduced the expression of TNF-α and IFN-γ mRNA, but not that of IL-10 and IL-4 mRNA. Reductions in TNF-α mRNA were correlated to clinical and endoscopic improvements, and normalization of TNF-α mRNA was obtained in patients with healed mucosa. The numbers of T lymphocytes and macrophages were significantly decreased in patients with healed mucosa after IFX treatment, although compared to normal controls, there were still increased levels of TNF-α-positive cells after treatment. Conclusions. IFX induced down-regulation of the mucosal TNF-α and IFN-γ mRNA expression in UC patients. The numbers of T lymphocytes and macrophages were significantly decreased in patients with endoscopically healed mucosa after IFX treatment.

• Cytokines
• immunohistochemistry
• inflammatory bowel disease
• quantitative real-time PCR