Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains

R. M. Peek, G. G. Miller, K. T. Tham, G. I. Perez-Perez, X. Zhao, J. C. Atherton, M. J. Blaser

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522 Scopus citations


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. EXPERIMENTAL DESIGN: To test the hypothesis that cagA+ strains 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-1β, IL-2, and IL-8 expression, and those infected with cagA+ compared with cagA- strains significantly more often expressed IL- 1α and IL-1β and showed elevated antral IL-8 protein levels. Similarly, patients with ulcer disease significantly more often expressed antral IL-1α 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.

Original languageEnglish (US)
Pages (from-to)760-770
Number of pages11
JournalLaboratory Investigation
Issue number6
StatePublished - 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


  • H. pylori
  • Inflammation
  • Peptic ulcer disease
  • cagA


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