The impact of IL‐1 deficiency in colitis‐mediated colon cancer

Inflammatory bowel diseases (IBD) predispose individuals to colon cancer. IL‐1, elevated during IBD, is implicated in cancer development in several models. Our objective was to determine the contribution of IL‐1 to carcinogenesis in a mouse model of colitis‐mediated colon cancer. Wildtype (WT), IL‐1R1 −/− and caspase‐1 −/− mice (n=6–12) were treated with azoxymethane (10 mg/kg) followed by 3 cycles of 3% dextran sulphate sodium. Unlike WT, IL‐1R1 −/− and caspase‐1 −/− mice had significant mortality (40–50%) after the second and third cycles, although inflammation severity in the mid‐colon did not differ between strains. All strains showed non‐invasive colon carcinoma. Cancer incidence did not differ significantly between strains (WT 60%, IL‐1R1 −/− 100% and caspase‐1 −/− 100%), however IL‐1R1 −/− mice had a higher tumor multiplicity compared to WT and caspase‐1 −/− mice (p<0.05). In conclusion, IL‐1R1 −/− and caspase‐1 −/− mice are more susceptible to chronic inflammation, despite histological inflammation scores that are similar to WT. Although cancer incidence did not differ between strains, the higher tumor number in IL‐1R1 −/− mice suggests a protective role for IL‐1 in this model. Funded by Crohn's and Colitis Foundation of Canada