Basic-alimentary tractProinflammatory effects of TH2 cytokines in a murine model of chronic small intestinal inflammation
Section snippets
Animals
SAMP1/YitFc mice were maintained under specific pathogen-free conditions at the Animal Facility of the University of Virginia. AKR and SCID (C3HSmn.C-Prkdcscid/J) mice were purchased from Jackson Laboratories (Bar Harbor, ME). All protocols were approved by the Animal Care and Use Committee of the University of Virginia.
Treatments
For IFN-γ neutralization, 3-week-old SAMP1/YitFc mice were treated weekly for 5 weeks with tail-vein injections of .5 mg of anti-mouse IFN-γ MAb (clone XMG-6, kindly provided by
Increased expression of TH2 cytokines in the terminal ileum of SAMP1/YitFc mice with chronic ileitis
To investigate the possible role of TH2 cytokines in the pathogenesis of chronic ileitis, we first performed quantitative mRNA analysis of cytokine gene expression in the terminal ileum of SAMP1/YitFc mice with long-standing inflammation (>30 weeks) in comparison with age-matched AKR controls and noninflamed SAMP1/YitFc cecal tissue. No significant differences in ileal IFN-γ or TNF expression between AKR and SAMP1/YitFc mice were observed in our study (data not shown). However, our results
Discussion
In the present study we report that both TH1- and TH2- mediated pathways contribute to the pathogenesis of ileitis in the SAMP1/YitFc mouse, a murine model of CD. We show that TH1 and TH2 cytokines participate in different stages of ileitis development and affect diverse components of the inflammatory response. We show that, during chronic ileitis, IFN-γ and IL-4 are not mutually exclusive but can act synergistically. Finally, we show that IL-4-producing Th lymphocytes are sufficient for the
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Cited by (0)
Supported by US Public Health Service/National Institutes of Health grants DK-42191, DK-44540, DK-55812 (to F.C.), and the University of Virginia Digestive Health Research Center (1P30DK67629). G.B. is a recipient of a Research Fellowship Award from the Crohn’s and Colitis Foundation of America.