title: Helicobacter pylori infection: mechanism of colonization and functional dyspepsia Reduced colonization of gastric mucosa by Helicobacter pylori in mice deficient in interleukin-10.
abstract: OBJECTIVE
  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 +/- 0.26CFU/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 < or = 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Wakefield Gastroenterology Research Laboratory, Wakefield Hospital, Newtown, Wellington, New Zealand. w.chen@clear.net.nz
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Shu
authors.forename: V S
authors.initials: VS
authors.lastname: Chadwick
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D005753:Gastric Mucosa / Q000382:microbiology*; D005756:Gastritis / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology / Q000502:physiology*; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D013234:Stem Cells / Q000502:physiology
chemical_list: D000907:Antibodies, Bacterial; D016753:Interleukin-10