IL-33 targeting attenuates intestinal mucositis and enhances effective tumor chemotherapy in mice

Guabiraba Brito, R. et al. (2014) IL-33 targeting attenuates intestinal mucositis and enhances effective tumor chemotherapy in mice. Mucosal Immunology, 7(5), pp. 1079-1093. (doi: 10.1038/mi.2013.124)

Full text not currently available from Enlighten.


Intestinal damage and severe diarrhea are serious side effects of cancer chemotherapy and constrain the usage of most such therapies. Here we show that interleukin-33 (IL-33) mediates the severe intestinal mucositis in mice treated with irinotecan (CPT-11), a commonly used cancer chemotherapeutic agent. Systemic CPT-11 administration led to severe mucosal damage, diarrhea, and body weight loss concomitant with the induction of IL-33 in the small intestine (SI). This mucositis was markedly reduced in mice deficient in the IL-33R (ST2−/−). Moreover, recombinant IL-33 exacerbated the CPT-11-induced mucositis, whereas IL-33 blockade with anti-IL-33 antibody or soluble ST2 markedly attenuated the disease. CPT-11 treatment increased neutrophil accumulation in the SI and adhesion to mesenteric veins. Supernatants from SI explants treated with CPT-11 enhanced transmigration of neutrophils in vitro in an IL-33-, CXCL1/2-, and CXCR2-dependent manner. Importantly, IL-33 blockade reduced mucositis and enabled prolonged CPT-11 treatment of ectopic CT26 colon carcinoma, leading to a beneficial outcome of the chemotherapy. These results suggest that inhibition of the IL-33/ST2 pathway may represent a novel approach to limit mucositis and thus improve the effectiveness of chemotherapy.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Besnard, Dr Anne-Gaelle and Guabiraba Brito, Dr Rodrigo and Graham, Professor Gerard
Authors: Guabiraba Brito, R., Besnard, A.-G., Menezes, G.B., Secher, T., Jabir, M.S., Amaral, S.S., Braun, H., Lima-Junior, R.C.P., Ribeiro, R.A., Cunha, F.Q., Teixeira, M.M., Beyaert, R., Graham, G.J., and Liew, F.Y.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Mucosal Immunology
Publisher:Nature Publishing Group
ISSN (Online):1935-3456

University Staff: Request a correction | Enlighten Editors: Update this record