pylori infection. When comparing H. pylori-infected children to adults, a clear pattern emerged whereby the children had a weaker drug discovery Th1 response. Although the density of H. pylori organisms was the same in children as compared to adults, the mean gastric concentration of IL-1 and TNF was significantly
higher in children. However, IL-2, IL-12, and IFN were significantly lower in children. In addition, the Th1 cytokines were noted to increase to adult levels by 18 years of age. As we continue to study and evaluate various vaccine strategies, a number of laboratories continue to focus on the mechanisms of protection following successful immunization. A study published in 2000 by Shirai et al. [47] suggested that salivary antibodies are a critical factor in successfully preventing H. pylori infection by vaccination. Ng et al. followed up and tried to confirm this observation by determining whether immune mediated Ku-0059436 mouse changes and/or mucin production were key factors in protection following immunization [5, 48]. Although they were able to confirm increased levels of salivary IgA as a result of immunizations, there was no increase
in mucin production or cytokine levels. Based on this study, the protection mechanism against H. pylori following immunization does not appear to be mediated by the cytokines within the salivary glands. There is much evidence confirming that chronic H. pylori infection results in the production of T-regulatory cells which play a role in its chronicity. Winter et al. [49] also recently demonstrated that the VacA and γ-glutamyl transferase found in membrane vesicles may also inhibit T cells from clearing this infection. The final study regarding the protection mechanism following H. pylori immunization contributes to a collection of reports demonstrating that promoting either Th1 or Th17 immunity is sufficient to protect mice from H. pylori. To the extent that the host
response to H. pylori infection is generally limited due to the induction of regulatory T cells, there is now considerable evidence that the key to inducing protection is to pre-empt or override regulatory T-cell activity by promoting Th1 and/or Th17 mediated immunity. Indeed, Ding et al. [50] demonstrated that it was possible to induce sterilizing immunity in infected mice through cytokine therapy with IL-12, even in the absence of immunization. click here A previous study by Velin et al. [51] achieved a reduction in bacterial load using a short-term IL-17 therapy. These findings may be particularly relevant in the continuing efforts to improve an H. pylori vaccine for use in humans. While the success achieved in murine models has not translated well in clinical trials, the results of Ding et al. indicate that a significant improvement may be achieved by the addition of cytokine adjuvants, or the development of pharmacologic agents able to specifically induce Th1 or Th17 cells in the absence of toxicity. H.