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P013. The effects of Schistosoma japonicum eggs antigen on SAMP1/Yit mice, a spontaneous ileitis model

T. Arai, T. Seki, T. Kumagai, R. Shimogawara, N. Ohta, Graduate School of Tokyo Medical and Dental University, Department of Environmental Parasitology, Bunkyo-ku, Japan

Background

It is known that the development of Crohn's disease (CD) is related to a polarized Th1 response.

Exposure to Schistosoma japonicum (SJ) eggs causes strong Th2 response, which is inhibitory against the Th1 response. Furthermore, it activates a network of regulatory T cells (Tregs) that secret interleukin-10. This cytokine down-regulate Th1 response in mice. Several studies showed that exposure to SJ eggs protected mice from experimental colitis. However, these experiments have been conducted with drug induced models, such as 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Considering that drug induced models are artificial and affect large bowel rather than small intestine, it is not suitable for studies on CD. A senescence-accelerated mouse (SAM) P1/Yit is a strain that develop spontaneous ileitis with 100% penetrance until 30 weeks of age, while losing its senescence accelerated phenotype. In this study, we investigated that whether exposure to SJ eggs prevent spontaneous ileitis.

Methods

Specific pathogen-free SAMP1/Yit mice were donated by the Yakult Central Institute for Microbiological Research (Tokyo, Japan). AKR/NSLc mice were used as control mice.

SJ eggs were collected from the liver of Schistosome-infected mice. The eggs were washed in phosphate buffered saline (PBS). Mice were injected with freeze-killed 5,000 eggs intraperitoneally once a week from 12 to 29 weeks of age. Control mice received PBS with the same volume. The effects of SJ eggs were quantified as follows: 1) body weight loss, 2) histological score of microscopic inflammation of ileum, 3) cytokines profiles of T-lymphocytes which are isolated from mesenteric lymph nodes (MLN). Statistical analyses were performed using Student's t test. P < 0.05 was considered to be statistically significant.

Results

1) SAMP1/Yit mice treatment with SJ eggs showed tendency to gain weight. 2) Histological score of ileitis was not modulated. 3) In the treatment group, the concentration of Interleukin (IL) 4 was increased significantly, however interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were not decreased and IL-10 was not increased compared to the control group.

Conclusion

This is the first report that investigated the effects of SJ eggs antigen on spontaneous ileitis model of CD. These findings suggest that treatment with SJ eggs did not attenuate ileitis, but increased body weight and the up-regulation of IL-4 suggest the therapeutic potentials of the parasite antigen for CD.