First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy

Atreya R, Billmeier U, Rath T, Mudter J, Neumann H, Neurath M, Vieth M (2015)

Publication Type: Journal article

Publication year: 2015

Journal

World Journal of Gastroenterology Baishideng Publishing Group Co. Limited

Book Volume: 21

Pages Range: 12963-9

Journal Issue: 45

DOI: 10.3748/wjg.v21.i45.12963

Abstract

We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies (infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6 (IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody (tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-?. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may lead to aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling.

Authors with CRIS profile

Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen (Heisenberg-Professur) Markus Neurath Lehrstuhl für Innere Medizin I Michael Vieth

Involved external institutions

Sana Kliniken Ostholstein DE Germany (DE) Klinikum Bayreuth DE Germany (DE)

How to cite

APA:

Atreya, R., Billmeier, U., Rath, T., Mudter, J., Neumann, H., Neurath, M., & Vieth, M. (2015). First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy. World Journal of Gastroenterology, 21(45), 12963-9. https://doi.org/10.3748/wjg.v21.i45.12963

MLA:

Atreya, Raja, et al. "First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy." World Journal of Gastroenterology 21.45 (2015): 12963-9.

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