Reduced colonization of gastric mucosa by Helicobacter pylori in mice deficient in interleukin‐101

Publisher Website
Google Scholar
Abstract
Background and Aims: Interleukin-10 (IL-10) is a potent anti-inflammatory and immunoregulatory cytokine. Mice deficient in IL-10 production (IL-10−/−mice) develop a spontaneous chronic enterocolitis, suggesting that IL-10 is an important regulator of the mucosal immune response in vivo. The objective of this study was to determine the role of endogenous IL-10 in the host defense against gastric colonization by Helicobacter pylori by using IL-10-deficient mice. Methods: The IL-10−/−mice were inoculated intragastrically with a mouse-adapted H. pylori isolate (Sydney Strain 1). Gastric colonization by H. pylori (biopsy urease test and bacterial colony counts), serum levels of H. pylori-specific immunoglobulin (Ig) M, A, G, isotypes of IgG, and the gastric mucosal inflammatory scores were determined 6 weeks after inoculation. Results were compared with those obtained from H. pylori-infected control mice (IL-10 +/−mice). Results: The colonization of gastric mucosa by H. pylori was reduced approximately 100-fold (P≤ 0.0001) in IL-10−/−mice (log10 4.87 ± 0.26 CFU/g tissue) as compared to IL-10+/−mice (log10 6.64 ± 0.22 CFU/g tissue). Furthermore, IL-10−/−mice infected with H. pylori had significantly higher H. pylori-specific IgA and IgG antibodies in serum (P≤ 0.01), and developed much more severe chronic active gastritis than infected IL-10+/−mice. The median scores of the infiltration of gastric mucosa by mononuclear cells and neutrophils were up to threefold higher in IL-10−/−mice than they were in IL-10+/−mice. Conclusion: Our studies suggest that endogenous IL-10 is an inhibitor of the protective immune response to H. pylori infection. Interleukin-10 participates in the downregulation of H. pylori-induced gastric inflammatory responses, which apparently confers a survival advantage to the organism promoting more effective colonization of gastric mucosa.