Supported by La Marató de TV3 Foundation; ref 03/1810 Ferring International; GETECCU-Otsuka; and the Spanish Ministry of Science and Innovation. BFU 200764887.
Apoptosis resistance of mucosal lymphocytes and IL-10 deficiency in patients with steroid-refractory Crohn's disease†
Article first published online: 8 NOV 2010
Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 17, Issue 7, pages 1490–1500, July 2011
How to Cite
Santaolalla, R., Mañé, J., Pedrosa, E., Lorén, V., Fernández-Bañares, F., Mallolas, J., Carrasco, A., Salas, A., Rosinach, M., Forné, M., Espinós, J. C., Loras, C., Donovan, M., Puig, P., Mañosa, M., Gassull, M. A., Viver, J. M. and Esteve, M. (2011), Apoptosis resistance of mucosal lymphocytes and IL-10 deficiency in patients with steroid-refractory Crohn's disease. Inflamm Bowel Dis, 17: 1490–1500. doi: 10.1002/ibd.21507
- Issue published online: 14 JUN 2011
- Article first published online: 8 NOV 2010
- Manuscript Accepted: 31 AUG 2010
- Manuscript Received: 26 JUL 2010
- lymphocyte apoptosis resistance;
- Crohn's disease;
- steroid resistance
Apoptosis resistance of T-cells is considered an abnormality of immune pathways in Crohn's disease (CD). It has been previously shown that corticosteroids induce apoptosis of cells involved in inflammation. Thus, our aim was to assess the apoptosis of mononuclear cells and pro/antiinflammatory cytokines in the intestinal mucosa of patients with active CD, related to steroid response, and identify cellular and molecular factors that may predict this response to therapy.
Patients with CD (n = 26), ulcerative colitis (UC) (n = 32), and controls (n = 10) were prospectively studied with mucosal biopsies before and 7–10 days after corticosteroid treatment. Immunophenotype and apoptosis of T and B lymphocytes, plasma cells, and macrophages were assessed by flow cytometry, immunohistochemistry, and immunofluorescence. The cytokine expression pattern was evaluated by quantitative polymerase chain reaction (PCR).
Apoptosis resistance of T and B lymphocytes was observed only in steroid-refractory and -dependent CD patients as compared to responsive patients (P = 0.032; P = 0.004, respectively), being evident after steroid treatment. Interleukin (IL)-10 was markedly increased at baseline in steroid-responsive patients compared to the nonresponders (P = 0.006; sensitivity: 88.8%; specificity: 66.6% to predict steroid response).
Apoptosis resistance of mucosal T and B cells in steroid-refractory and -dependent CD patients appears during the evolution of the acute phase, limiting its clinical application as a predictor marker. In contrast, increased expression of IL-10 at an early stage of active steroid-sensitive CD patients supports its usefulness at predicting a good steroid response. Steroid-dependent and -refractory CD patients share similar molecular and cellular pathophysiological mechanisms. (Inflamm Bowel Dis 2010;)