Dextran sodium sulphate-induced colitis activity varies with mouse strain but develops in lipopolysaccharide-unresponsive mice

Bacteria and their products have been implicated in the pathogenesis of chr onic Inflammatory Bowel disease. The aim of this study was to investigate t he potential role of lipopolysaccharides (LPS) in the development of intest inal injury by comparing the effects of the dextran sodium sulphate (DSS)-i nduced model of colitis in LPS-sensitive and -insensitive mice. Experimenta l colitis was induced in LPS-sensitive mice (C3H/He) and their LPS-insensit ive congenic strain (C3H/HeJ). Colitis was assessed clinically using a dise ase activity index (derived from the three main clinical signs; diarrhoea, rectal bleeding and weight loss) and by histological scoring of the disease d colon. The clinical signs and disease activity index did not differ betwe en the LPS-sensitive and -insensitive costrains. Similarly, histological sc ores did not differ significantly fur either C3H strain at any time point d uring exposure to DSS. However, there were differences in the inflammatory response when different strains were compared (C3H vs CBA): the effects of DSS in C3H mice were immediate, more severe and mainly involved che caecum and ascending colon. These findings suggest that LPS from colonic bacteria do not play a primary role in the initiation of DSS-induced colitis and dem onstrate clear differences in the responsiveness of different mouse strains to DSS.