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099 VAGAL INTEGRITY AND EXPERIMENTAL COLITIS JE Ghia, P Blennerhassett, SM Collins Previous studies have identified a counter-inflammatory vagal reflex in the context of endotoxic shock. We have extended this observation to show that the vagus confers protection against both acute (5 days) and chronic (58 days) colitis induced by dextran sodium sulfate (DSS). We have shown that this is mediated via macrophages and involves the suppression of pro-inflammatory cytokines.
Intestinal Diseases Research Programme, Health Science Center, McMaster University, Hamilton, Ontario
In this study, we have examined whether the vagal integrity confers long lasting protection by studying DSS-induced inflammatory responses in the colon at 14 to 66 days post-vagotomy. The integrity of vagotomy was confirmed at all time points using CCK-induced satiety.
As previously described, vagotomy associated with the pyloroplasty increased all measured indices of inflammation. Vagotomy increased the disease activity index, macroscopic and histological scores by 75% and 41% respectively. In addition, MPO activity, serum levels of CRP and colonic tissue levels of pro-inflammatory cytokine when colitis was induced 9 days post-vagotomy. However, these increases in inflammatory indices were substantially diminished in mice with colitis induced 21, 33 and 61 days post-vagotomy. This was accompanied by increased production of IL-10, TGF-beta and an increase in FOXP3 staining in colonic tissue and increased serum corticosterone.
These findings indicate that while vagal integrity is an important protective factor, other counter inflammatory mechanisms, that may involve regulatory T cells, come into play if vagal integrity is compromised beyond 2 weeks.