Levels of interleukin-18 are markedly increased in Helicobacter pylori-infected gastric mucosa among patients with specific IL18 genotypes

J Infect Dis. 2008 Jun 15;197(12):1752-61. doi: 10.1086/588196.

Abstract

Background: The cellular immune response in gastric mucosa infected with Helicobacter pylori is proposed to be predominantly of the T helper cell type 1 type.

Methods: Interleukin (IL)-18, IL-12, and interferon (IFN)-gamma levels were measured in gastric mucosal biopsy specimens by reverse-transcription polymerase chain reaction (PCR) and by enzyme-linked immunosorbent assay; IL18 polymorphisms were determined by PCR.

Results: Biopsy specimens from 128 patients (56 with nonulcer dyspepsia, 28 with gastric ulcers, 28 with duodenal ulcers, and 16 with gastric cancer) were examined; 96 patients had H. pylori infection. IL-18 levels were markedly up-regulated in mucosa infected with H. pylori (P < .001), whereas IL-12 and IFN-gamma levels were independent of H. pylori status. IL-18 levels correlated with IFN-gamma levels only in infected patients (R = 0.31 to R = 0.51). IL-18 levels were the determining factor for monocyte infiltration in H. pylori-infected mucosa (P < .001). H. pylori-infected patients displaying IL18 -607C/C and -137G/G had higher IL-18 levels than did those with other genotypes and were more likely to experience treatment failure.

Conclusion: H. pylori infection induces IL-18 in the gastric mucosa. H. pylori-infected patients with IL18 -607C/C and -137G/G have higher IL-18 levels, which causes severe gastric inflammation. IL18 genotype might be a marker for predicting the effects of eradication therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use
  • Duodenal Ulcer / genetics
  • Duodenal Ulcer / microbiology
  • Dyspepsia / genetics
  • Dyspepsia / microbiology
  • Female
  • Gastric Mucosa / immunology
  • Gastric Mucosa / microbiology*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genotype
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / metabolism*
  • Helicobacter pylori*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-18 / genetics*
  • Interleukin-18 / metabolism*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / microbiology
  • Stomach Ulcer / genetics
  • Stomach Ulcer / microbiology

Substances

  • Anti-Bacterial Agents
  • Genetic Markers
  • Interleukin-18
  • Interleukin-12
  • Interferon-gamma