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

Lab Invest. 1995 Dec;73(6):760-70.


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+ 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.

Conclusion: 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Bacterial*
  • Bacterial Proteins / physiology*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / microbiology*
  • Gastritis / microbiology*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Interleukin-1 / biosynthesis*
  • Interleukin-1 / genetics
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis


  • Antigens, Bacterial
  • Bacterial Proteins
  • Interleukin-1
  • Interleukin-8
  • RNA, Messenger
  • cagA protein, Helicobacter pylori