BACKGROUND & AIMS: Infliximab is a monoclonal antibody against tumor necrosis factor that is used to treat patients with inflammatory bowel disease. We investigated serum levels and cellular expression of interleukin (IL)-15 and its receptor (sIL-15Ralpha) in patients with Crohn's disease (CD) treated with infliximab; and the effect on sIL-15Ralpha secretion by epithelial cells. METHODS: CD patients were given infliximab (n = 40; 3 infusions); 37 healthy controls were studied. Serum levels of IL-15, sIL-15Ralpha, and complex were determined by radioimmunoassay and cytokine levels by enzyme-linked immunosorbent assay. IL-15Ralpha and A Desintegrin and Metalloproteinase 17 levels were assessed by immunohistochemistry. Epithelial cell lines (HT-29 and Caco-2) were cultured with infliximab, adalimumab, or etanercept. Patients were classified as responders and nonresponders according to their Crohn's Disease Activity Index and clinical observations. RESULTS: Before infliximab, IL-15 was higher in responders than in controls and nonresponders. After infliximab, IL-15 decreased in responders while remaining stable in nonresponders. sIL-15Ralpha and IL-15/sIL-15Ralpha complex levels were higher in CD than in controls and increased only in responders after infliximab. IL-15Ralpha and A Desintegrin and Metalloproteinase 17 colocalized in epithelial cells and were higher in CD patients. In vitro, infliximab but not adalimumab and etanercept induced sIL-15Ralpha secretion by epithelial cells. CONCLUSIONS: Serum level of sIL-15Ralpha and the IL-15/sIL-15Ralpha complex increased in responder patients and the response was associated with a decrease of IL-15. Infliximab induced the release of the IL-15 receptor alpha, suggesting a specific modulation of IL-15 and its soluble receptor by reverse signaling through transmembrane tumor necrosis factor alpha. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
BACKGROUND & AIMS:Infliximab is a monoclonal antibody against tumornecrosis factor that is used to treat patients with inflammatory bowel disease. We investigated serum levels and cellular expression of interleukin (IL)-15 and its receptor (sIL-15Ralpha) in patients with Crohn's disease (CD) treated with infliximab; and the effect on sIL-15Ralpha secretion by epithelial cells. METHODS:CDpatients were given infliximab (n = 40; 3 infusions); 37 healthy controls were studied. Serum levels of IL-15, sIL-15Ralpha, and complex were determined by radioimmunoassay and cytokine levels by enzyme-linked immunosorbent assay. IL-15Ralpha and A Desintegrin and Metalloproteinase 17 levels were assessed by immunohistochemistry. Epithelial cell lines (HT-29 and Caco-2) were cultured with infliximab, adalimumab, or etanercept. Patients were classified as responders and nonresponders according to their Crohn's Disease Activity Index and clinical observations. RESULTS: Before infliximab, IL-15 was higher in responders than in controls and nonresponders. After infliximab, IL-15 decreased in responders while remaining stable in nonresponders. sIL-15Ralpha and IL-15/sIL-15Ralpha complex levels were higher in CD than in controls and increased only in responders after infliximab. IL-15Ralpha and A Desintegrin and Metalloproteinase 17 colocalized in epithelial cells and were higher in CDpatients. In vitro, infliximab but not adalimumab and etanercept induced sIL-15Ralpha secretion by epithelial cells. CONCLUSIONS: Serum level of sIL-15Ralpha and the IL-15/sIL-15Ralpha complex increased in responder patients and the response was associated with a decrease of IL-15. Infliximab induced the release of the IL-15 receptor alpha, suggesting a specific modulation of IL-15 and its soluble receptor by reverse signaling through transmembrane tumornecrosis factor alpha. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Authors: Clémentine Perrier; Ingrid Arijs; Dominiek Staelens; Christine Breynaert; Isabelle Cleynen; Kris Covens; Marc Ferrante; Gert Van Assche; Séverine Vermeire; Gert de Hertogh; Frans Schuit; Paul Rutgeerts; Jan L Ceuppens Journal: Immunology Date: 2013-01 Impact factor: 7.397
Authors: Grégory Bouchaud; Samuel Gehrke; Carsten Krieg; Antonios Kolios; Jürg Hafner; Alexander A Navarini; Lars E French; Onur Boyman Journal: J Exp Med Date: 2013-09-09 Impact factor: 14.307
Authors: Simon A Hirota; Aito Ueno; Sarah E Tulk; Helen M Becker; L Patrick Schenck; Mireille S Potentier; Yan Li; Subrata Ghosh; Daniel A Muruve; Justin A MacDonald; Paul L Beck Journal: Mediators Inflamm Date: 2016-08-17 Impact factor: 4.711