Atreya R, Billmeier U, Rath T, Mudter J, Vieth M, Neumann H, Neurath MF. First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy. World J Gastroenterol 2015; 21(45): 12963-12969 [PMID: 26668517 DOI: 10.3748/wjg.v21.i45.12963]
Corresponding Author of This Article
Markus F Neurath, MD, Professor of Medicine, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, Ulmenweg 18, D-91054 Erlangen, Germany. markus.neurath@uk-erlangen.de
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Case Report
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Atreya R, Billmeier U, Rath T, Mudter J, Vieth M, Neumann H, Neurath MF. First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy. World J Gastroenterol 2015; 21(45): 12963-12969 [PMID: 26668517 DOI: 10.3748/wjg.v21.i45.12963]
World J Gastroenterol. Dec 7, 2015; 21(45): 12963-12969 Published online Dec 7, 2015. doi: 10.3748/wjg.v21.i45.12963
First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy
Raja Atreya, Ulrike Billmeier, Timo Rath, Jonas Mudter, Michael Vieth, Helmut Neumann, Markus F Neurath
Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, Germany
Jonas Mudter, Medical Department, Hospital Ostholstein, 23701 Eutin, Germany
Michael Vieth, Institute of Pathology, Klinikum Bayreuth, 95445 Bayreuth, Germany
Author contributions: Atreya R and Neurath MF designed the study; Atreya R, Billmeier U, Rath T, Mudter J, Vieth M, Neumann H and Neurath MF acquired the data; Atreya R, Billmeier U, Vieth M, Neumann H, Neurath MF analyzed the data; Atreya R, Billmeier U, Rath T, Mudter J, Vieth M, Neumann H and Neurath MF interpreted the data and wrote the paper.
Supported by Clinical Research Group 257 CEDER of the Deutsche Forschungsgemeinschaft.
Institutional review board statement: Ethics approval has been granted by the Ethics Committee of the Friedrich-Alexander Universität Erlangen-Nürnberg. It has approved analysis of the mucosal biopsies. The anti-IL-6R antibody (tocilizumab) was applied as compassionate use therapy in a patient with treatment refractory ulcerative colitis.
Informed consent statement: The patient provided informed written consent prior to study enrolment.
Conflict-of-interest statement: The authors declare no conflict-of-interest
Correspondence to: Markus F Neurath, MD, Professor of Medicine, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, Ulmenweg 18, D-91054 Erlangen, Germany. markus.neurath@uk-erlangen.de
Telephone: +49-9131-8535000 Fax: +49-9131-8535209
Received: March 29, 2015 Peer-review started: March 30, 2015 First decision: June 2, 2015 Revised: June 30, 2015 Accepted: September 14, 2015 Article in press: September 14, 2015 Published online: December 7, 2015 Processing time: 252 Days and 6.6 Hours
Core Tip
Core tip: Interleukin (IL)-6 is regarded as a pro-inflammatory cytokine in the immunopathogenesis of inflammatory bowel diseases. Unexpectedly, this first reported case describes that anti-IL-6R antibody treatment led to aggravated inflammation in a severe ulcerative colitis patient. Mechanistic studies revealed that anti-IL-6R treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines. Our case report demonstrates that differential responsiveness of target cells has to be taken into account in therapeutic approaches, as IL-6 promotes mucosal inflammation via soluble IL-6R signaling, but also strongly contributes to epithelial cell survival via mIL-6R signaling.
