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

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.