title: Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains.
abstract: BACKGROUND
  Helicobacter pylori strains that possess the cytotoxin-associated gene (cagA) are highly associated with peptic ulcer disease, but the role of cagA in pathogenesis is unknown.
  
  
  METHODS
  To test the hypothesis that cagA+ stains elicit a greater proinflammatory cytokine response in the gastric mucosa than cagA- strains, gastric biopsies were obtained from 52 patients and studied by histology, culture, enzyme-linked immunosorbent assay, and reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Of 52 patients, 32 (62%) were infected with H. pylori based upon both serology and histology or culture, 16 (31%) were negative by serology, histology, and culture, and four (7%) were positive by serology only. Of 15 H. pylori-infected patients with peptic ulceration, 14 (92%) were infected with cagA+ strains compared with 8 (50%) of 16 patients with gastritis alone, and those infected with cagA+ strains had significantly higher grades of inflammation in the gastric mucosa. Antral inflammation score was significantly associated with IL-8 production. Antral biopsies from infected patients, compared with uninfected patients, significantly more often demonstrated IL-1 beta, IL-2, and IL-8 expression, and those infected with cagA+ compared with cagA- strains significantly more often expressed IL-1 alpha and IL-1 beta and showed elevated antral IL-8 protein levels. Similarly, patients with ulcer disease significantly more often expressed antral IL-1 alpha and IL-8 than those without ulceration.
  
  
  CONCLUSIONS
  These results indicate that infection with cagA+ H. pylori strains is associated with higher grades of gastric inflammation, correlating with enhanced mucosal levels of IL-8, and increased risk of peptic ulceration.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Peek
authors.forename: G G
authors.initials: GG
authors.lastname: Miller
authors.forename: K T
authors.initials: KT
authors.lastname: Tham
authors.forename: G I
authors.initials: GI
authors.lastname: Perez-Perez
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: J C
authors.initials: JC
authors.lastname: Atherton
authors.forename: M J
authors.initials: MJ
authors.lastname: Blaser
mesh_terms: D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000502:physiology*; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology*; D005756:Gastritis / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; C080866:cagA protein, Helicobacter pylori