Celecoxib and rofecoxib potentiate chronic colitis and premalignant changes in interleukin 10 knockout mice

Nonsteroidal anti‐inflammatory drugs decrease sporadic colorectal carcinoma and adenomas in patients with familial adenomatous polyposis and in rodent models of sporadic colon cancer and familial adenomatous polyposis. Similarly, selective cyclooxygenase 2 inhibitors decrease adenomas in humans and rodents. However, their effects on chronic colitis and colitis‐associated neoplasia are unknown. Interleukin 10−/− mice (C57/B6) were fed regular chow (n = 20) or chow with celecoxib (1,500 ppm, n = 18) or rofecoxib (75 ppm, n = 20) for 12 weeks. Twenty‐eight percent of the celecoxib group died versus 5% of the control and rofecoxib groups (p < 0.05 compared with control). Celecoxib and rofecoxib increased the incidence of colitis (26% vs. 92% and 68%, p < 0.01), colitis score (0.4 ± 0.2 vs. 2.5 ± 0.3 and 2 ± 0.4, p < 0.01), aberrant crypt foci (0.5 ± 0.3 vs. 3.7 ± 2.6 and 2.8 ± 0.7, p < 0.01), aberrant crypts per mouse (4.11 ± 2.1 vs. 41.2 ± 9.7 and 27.1 ± 7.5, p < 0.01) and dysplasia (11% vs. 54% and 42%, p < 0.01). Similarly, indomethacin (9 ppm, n = 15) increased colitis score, aberrant crypt foci, and dysplasia after 27 days of treatment. Two selective cyclooxygenase 2 inhibitors exacerbate colitis and premalignant changes in the interleukin 10−/− mouse model of chronic colitis and colitis‐associated colon carcinoma.