Effect of Infliximab on IFN-γ and IL-4 Expression in Peripheral Blood and Inflamed Intestinal Mucosa of Patients with Crohn’s Disease

Ivan Ferkolj¹*, Saša Marković¹, @eljka Većerić¹, Alojz Ihan², Maja Pohar³

¹ University Medical Centre Ljubljana, Division of Internal Medicine, Department of Gastroenterology, Ljubljana, Slovenia
² Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia
³ Institute of Biomedical Informatics, Faculty of Medicine, University of Ljubljana, Slovenia
Tel: +386 41 519879,
Fax: +386 1 4334190,
E-mail: ivan.ferkolj@kclj.si

Abstract
Background: Infliximab, a monoclonal anti-tumor necrosis factor alpha (TNF-α) antibody, is an effective treatment for  Crohn’s disease without prior response to conventional therapy. It binds with high affinity to soluble and membranebound TNF-α, neutralizing its biological activity and reducing TNF-α 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-γ) 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-γ 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-γ 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-γ 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-α, which resulted in silencing of the inflammation.

Keywords: Crohn’s disease, infliximab, interferon-gamma, interleukin-4