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Neonatal Co-Infection with Helicobacter Species Markedly Accelerates the Development of Inflammation-Associated Colonic Neoplasia in IL-10−/–Mice


Reprint requests to: Laura P. Hale, MD PhD, Box 3712, Duke University Medical Center, Durham, NC 27710, USA Tel.: [919] 684-4771; Fax: [919] 684-4445; E-mail:


Background:  Inflammatory bowel disease (IBD) is hypothesized to represent an aberrant immune response against enteric bacteria that occurs in a genetically susceptible host. Humans and mice with IBD are at markedly increased risk for colonic neoplasia. However, the long lead time required before development of inflammation-associated colon neoplasia in commonly used murine models of IBD slows the development of effective chemopreventative therapies.

Materials and methods:  Neonatal coinfection with Helicobacter typhlonius and Helicobacter rodentium was used to trigger the onset of IBD in mice deficient in the immunoregulatory cytokine interleukin (IL)-10. The severity of colon inflammation and incidence of neoplasia was determined histologically.

Results:  IL-10−/– mice demonstrated early onset, severe colon inflammation following neonatal infection with H. typhlonius and H. rodentium. The incidence of inflammation-associated colon neoplasia was ~95% at a mean age of 21 ± 2 weeks. Mutation of endoglin, an accessory receptor for TGF-β, did not affect the severity of IBD or the incidence of neoplasia in this model.

Conclusions:  The rapid onset of severe colon inflammation and multiple neoplastic lesions in the colons of IL-10−/– mice neonatally coinfected with H. typhlonius and H. rodentium makes this model well-suited for investigating the mechanisms involved in inflammation-associated colon cancer as well as its chemoprevention.

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