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- W1454367246 abstract "Introduction: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract with a poorly understood pathogenesis. Vasoactive Intestinal Peptide (VIP) has been shown to play a potent anti-inflammatory effect In Vitro, by inhibiting the release of Th1 pro-inflammatory cytokines from T cells and macrophages. Thus, our expectation is that the use of a VIP antagonist or deletion of the VIP gene in mice would lead to an increase in inflammation. To investigate this hypothesis further In Vivo, we have utilized the well characterized Dextran Sulfate Sodium (DSS) colitis model, to study the development of colonic inflammation in wild type (WT) mice, with or without the administration of VIP partial antagonist (VIPHybrid) and in VIP-/deficient mice. Methods: Colitis was induced in 8 adult (WT), and 8 adult VIP -/deficient, C57BL/6 mice with 2.5% DSS given orally for 5 days. Intraperitoneal (ip) injections of 2.3 ug (100uM) VIPHybrid (Phoenix) or vehicle were administered daily to the WT mice. Measurements of water intake, body weight, observations of activity and stool appearance were made at baseline and daily thereafter for eleven consecutive days. On the 11th day the animals were sacrificed and the intact colon from each mouse was dissected, examined macroscopically, the weight and length were measured and their ratio was scored in a blinded fashion. The myeloperoxidase (MPO) assay was performed on samples from the proximal and distal colon for each mouse. Results: WT mice, treated with vehicle showed the greatest loss in body weight (11.5%) compared to the mice treated with VIPHybrid (8.9%, p<0.05) or VIP -/(1.4%, p<0.001). The colonic length to weight ratio was significantly lower in the VIPHybrid treated group (2.9, p<0.05) and VIP -/group (3.0, p<0.01) compared to the vehicle treated group (3.7). MPO assay and histological analysis on H&E stained cut tissue slides performed on proximal and distal colonic samples confirmed the lower values of the inflammatory parameters observed in VIP-/and in VIPHybrid treated WT mice groups. Conclusions: DSS-treated VIP deficient mice exhibited significantly lower levels of inflammatory parameters, compared to WT mice. WT mice treated with VIPHybrid also demonstrated lower inflammatory parameters than untreated WT mice. These results demonstrate that VIP antagonism as shown by both using a VIP receptor antagonist or in VIP deficient mice leads to a reduction in colonic inflammation. Thus, VIP antagonists such as VIPHybrid may provide to be a useful strategy to reduce colonic inflammation in conditions such as inflammatory bowel disease and deserve further investigation." @default.
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- W1454367246 date "2012-05-01" @default.
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- W1454367246 title "Mo1110 VIP Antagonism Has an Anti-Inflammatory Effect in Dextran Sulfate Sodium (DSS)-Induced Colitis" @default.
- W1454367246 doi "https://doi.org/10.1016/s0016-5085(12)62290-2" @default.
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