title: Acute blockade of IL-25 in a colitis associated colon cancer model leads to increased tumor burden.
abstract: Chronic inflammation within the gastrointestinal tract results in an increased risk for developing colorectal cancer. Epithelial cytokines, including interleukin-25 (IL-25), are produced in the colon and are critical for protection from parasites, but can also be pathogenic in the context of inflammatory bowel diseases and allergy. Whether IL-25 is involved in the progression from inflammation to cancer is still largely unexplored. Using a well-established murine model for colitis-induced colon cancer; we aimed to determine the role of IL-25 in this process. We found that acute IL-25 blockade resulted in greater tumor burdens compared to isotype control treated mice. Histologically, α-IL-25 treated mice had increased colitis scores compared to mice receiving isotype control antibody, as well as decreased eosinophilia. This is the first study to explore the therapeutic potential of using an IL-25 blocking antibody during a chronic inflammatory setting. Taken together these data suggest that IL-25 plays an inhibitory role in the growth and development of colonic tumors.
authors.affiliation: Immunology Program, Benaroya Research Institute, Seattle, Washington, USA.|Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Tennille D
authors.initials: TD
authors.lastname: Thelen
authors.affiliation: Immunology Program, Benaroya Research Institute, Seattle, Washington, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Green
authors.affiliation: Immunology Program, Benaroya Research Institute, Seattle, Washington, USA.|Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001397:Azoxymethane; D003092:Colitis / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000378:metabolism; D008807:Mice, Inbred BALB C; D047368:Tumor Burden
chemical_list: D057134:Antibodies, Neutralizing; D020381:Interleukin-17; D016264:Dextran Sulfate; D001397:Azoxymethane