Murine model of intestinal ricin intoxication: Evidence for widespread epithelial damage and coincident production of monocyte chemotactic protein-1. [Infect Immun] Journal article

The development of small animal models is necessary to understand host responses and immunity to emerging infectious diseases and potential bioterrorism agents. In this report we have characterized a murine model of intestinal ricin intoxication. Ricin administered intragastrically (i.g.) to BALB/c mice at doses ranging from 1 to 10 mg/kg induced dose-dependent morphological changes in the proximal small intestine (i.e., duodenum), including widespread villus atrophy and epithelial damage. Coincident with epithelial damage was a localized increase in monocyte chemotactic protein-1 (MCP-1), a chemokine known to be associated with inflammation of the intestinal mucosa. Immunity to intestinal ricin intoxication was achieved by immunizing mice i.g. with ricin toxoid, and correlated with elevated levels of anti-toxin mucosal IgA and serum IgG antibodies. We conclude that the mouse model we have developed will serve as a valuable tool in identifying the inflammatory pathways and protective immune responses that are elicited in the intestinal mucosa following ricin exposure, and will prove useful in the evaluation of anti-toxin vaccines and therapeutics.

Infect Immun