Leslie, F.C.; McDermott, J.R.; Kazmi, S.; Grencis, R.; Thompson, D.G.; McLaughlin, J.T.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA15
Academic Journal
The mechanisms by which small intestinal infection and inflammation produce symptoms such as anorexia are poorly understood. Upregu-lation of enteroendocrine (EEC) cell function is a plausible mechanism, because regulatory peptides/amines, for example CCK and 5HT, regulate food intake. Trichinella spiralis infection in mice is a well described model of small intestinal inflammation, and has been proposed as an animal model of postinfective functional Gl disorders. Effects on feeding and EEC have not been assessed. Methods: Male NIH mice were infected with 300 T spiralis larvae by oral gavage. Food intake was measured and compared with a control group of naive mice. On days 6, 9, 13, and 20 postinfection (PI), duodena were fixed and immunostained for 5HT and CCK. Results are expressed as numbers of positive staining EEC per 15 crypt/villus units. To assess the contribution of the mast cell infiltration seen in this model, an anti c-Kit antibody (Ack-2) was administered i.p. to attenuate mast cell responses. A control group received nonspecific IgG. Results: Six days PI, increased numbers of CCK-positive EEC cells were seen (9.0±1.3) compared to naive mice (6.7±0.7, p = 0.03). This peaked from day 9 (15.3±1.7, p < 0.01) to day 13 (15.0±0.6, p < 0.01) but improved by day 20 (8.5±0.9, p = ns), when inflammation has resolved. Similar changes were seen with 5HT-positive EEC cells, although not significantly increased until day 9 (19.8±2.6, p < 0.01) and day 13 (17.0±0.9, p = < 0.01). This again resolved by day 20 (7.2±1.5, p = ns). Food intake dropped from 4.5±0.1 g/mouse/day in naive mice to 3.4±0.5 at day 7, to 2.1±0.8 at day 9, and to 3.1±0.2 at day 11 (all p < 0.05). This normalised by day 14. Studies following Ack-2 showed that hypophagia and increased EEC persist despite effective mast cell attenuation. Conclusions: Acute small intestinal infection is associated with an increase...


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