Effect of infliximab on IFN-γ and IL-4 expression in peripheral blood and inflamed intestinal mucosa of patients with Crohn's disease

Background: Infliximab, a monoclonal anti-tumor necrosis factor alpha (TNF-alpha) antibody, is an effective treatment for Crohn's disease without prior response to conventional therapy. It binds with high affinity to soluble and membrane-bound TNF-alpha, neutralizing its biological activity and reducing TNF-alpha production by mucosal cells. Its influence on other cytokines has been investigated to a much smaller extent. Aim: The aim of the study was to establish the influence of infliximab on cells containing the proinflammatory cytokine interferon-gamma (IFN-gamma) and the anti-inflammatory cytokine interleukin- 4 (IL-4) in peripheral blood and inflamed intestinal mucosa. Methods: Twenty-five patients with Crohn's disease (11 with the luminal and 14 with the fistular form) underwent treatment with infliximab. IFN-gamma and IL-4 containing cells in peripheral blood and inflamed intestinal mucosa were analysed by flow cytometry before and 14 days after the treatment. Results: Twenty-two patients (88%) showed a clinical response to the drug and three (12%) had no response. In the group of responders, the proportion of cells containing IFN-gamma and IL-4 in peripheral blood and inflamed intestinal mucosa remained unchanged after the treatment. Conclusions: Infliximab has no direct influence on cells containing IFN-gamma and IL-4 in peripheral blood and inflamed intestinal mucosa. The insignificant changes in the proportions of these cells observed after the treatment may be attributed to its direct effect on TNF-alpha, which resulted in silencing of the inflammation.