1. FRI077 Jejunal dysmotility in a food allergy mouse model Jørgen Valeur 1, Jani Lappalainen 2, Hannu Rita 3, Aung Htun Lin 1, Petri T. Kovanen 2, Arnold Berstad 1, Kari Eklund 4 & Kirsi Vaali 1 1 Institute of Medicine, University of Bergen, Norway, 2 Atherosclerosis Group, Wihuri Research Institute, Finland, 3 Faculty of Agriculture and forestry, Statistics and Methodology, University of Helsinki, Finland, 4 Department of Rheumatology, Helsinki University Central Hospital, Finland A METHODS Balb/c mice were epicutaneously sensitized with ovalbumin for two week periods. They were challenged every second day from day 38 with 10 intragastric ovalbumin doses (50 mg/mouse) (fig 1). Stool consistency was evaluated before and after challenges with ovalbumin. Smooth muscle contractility of isolated circular jejunal sections was studied in organ bath equipment with increasing concentrations of carbamylcholine chloride (carbachol). Smooth muscle layer thickness was assayed from cross-sectional histological cuttings. Cytokine expression levels were studied from jejunal and ileal tissue sections with quantitative real-time PCR. CONCLUSIONS In this mouse model of food allergy, we demonstrated altered muscular response towards a muscarinic agonist, and increased levels of Th2-, but not Th1-mediated cytokine mRNAs, in jejunum. Serum immunoglobulin levels correlated with the number of jejunal mast cells (mucosal mast cell protease 1 (MMCP-1) positive cells) and serum MMCP-1, and predicted diarrhoea. The overall change may reflect a protective mechanism of the gut in food allergy. AIMS We hypothesized that food allergy causes a state of non-specific jejunal dysmotility. We tested this in an animal model (Vaali K et al 2006), where allergy was induced by repeated administrations of ovalbumin without immunostimulating adjuvant to wounded skin, followed by intragastric challenges with the same protein. Reference Vaali K, Puumalainen TJ, Lehto M et al. Murine model of food allergy after epicutaneous sensitization: role of mucosal mast cell protease-1. Scand J Gastroenterol 2006; 12: 1405-13 Reference Vaali K, Puumalainen TJ, Lehto M et al. Murine model of food allergy after epicutaneous sensitization: role of mucosal mast cell protease-1. Scand J Gastroenterol 2006; 12: 1405-13 RESULTS Ovalbumin-specific IgE correlated with jejunal mast cell countings (fig 2). In the allergic mice, higher doses of carbachol were required to reach half-maximal stimulation of circular muscle, especially in mice with diarrhoea (fig 3). This decreased sensitivity to carbachol was associated with increased expression of IL-4 and IL-6 mRNA in jejunum, but not in ileum (fig 4). Thickness of smooth muscle layers, as well as IFN- , TNF-  and TGF-  1 expressions, were not affected. FIGURES Figure 3 The smooth muscle organ bath arrangement (A), used to obtain the contractility curves (B). Allergic mice with diarrhoea (●, n = 5) showed a hypocontractile response of the circular muscle compared to controls (○, n = 5), P = 0.048 using curve slope analysis. Figure 4 Cytokine mRNA expression levels in jejunal and ileal tissues. Th2 mediated cytokine levels were significantly increased in jejunal samples from allergic mice ( P < 0.001), but not significantly different in ileal samples. AB Figure 1 The murine food allergy model: sensitization and challenge procedure. Epicutaneous sensitizations were performed twice in 1 week intervals, intragastric challenges were performed 10 times from day 38. Figure 2 A: Jejunal mast cells (mucosal mast cell protease 1 (MMCP-1) positive cells) correlated to serum ovalbumin- specific IgE. Pearson r = 0.708, P = 0.007. B: Serum MMCP-1 correlated to serum ovalbumin-specific IgE. Pearson r = 0.819, P = 0.0006.