Interleukin-27 is abrogated in gastric cancer, but highly expressed in other Helicobacter pylori-associated gastroduodenal diseases

Helicobacter. 2020 Feb;25(1):e12667. doi: 10.1111/hel.12667. Epub 2019 Nov 8.

Abstract

Background: IL-27 has dual roles in the immune response either stimulating Th1 or inhibiting Th17 cells. Because there is a particular link of IL-23/Th17 axis in the development of cancer and IL-27 has been considered a potential treatment for cancer, we evaluated the gastric and serum concentrations of IL-27 in two mutually exclusive Helicobacter pylori-associated diseases, gastric cancer (GC) and duodenal ulcer (DU).

Material and methods: We prospectively studied 110 H pylori-positive patients and 40 healthy blood donors. Serum and gastric concentrations of IL-27 and cytokines of the Th1/Th17 cells were assessed by ELISA.

Results: IL-27 was not detected in GC patients, but the cytokine concentration was very high in the patients with DU. IL-27 was also detected in the gastritis patients and in the H pylori-positive blood donors. IL27RA mRNA expression in peripheral blood mononuclear cells, evaluated by rt-PCR, was stimulated by H pylori strains. The cytokine concentration positively correlated with the Th1 and negatively with Th17 cell representative cytokine levels. Gastric IL-27 concentrations were positively correlated with increased degree of mononuclear and polymorphonuclear cells on the antral gastric mucosa of DU patients in consonance with the DU gastritis pattern. IL-12p70 and IFN-γ gastric concentrations were significantly higher in DU than in GC. Conversely, gastric concentrations of Th17 cell-associated cytokines (IL-1β, IL-6, IL-17A, IL-23, and TGF-β) were significantly higher in GC than in DU patients.

Conclusion: Although H pylori infection is able to elicit IL-27 and IL-27Rα secretion, DU and GC have diametrically opposed cytokine patterns.

Keywords: Helicobacter pylori; IL-27; Th1; Th17 cytokines; duodenal ulcer; gastric cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Duodenal Ulcer / genetics
  • Duodenal Ulcer / immunology
  • Duodenal Ulcer / microbiology
  • Female
  • Helicobacter Infections / genetics*
  • Helicobacter Infections / immunology
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / genetics
  • Helicobacter pylori / physiology*
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukin-27 / genetics*
  • Interleukin-27 / immunology
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Prospective Studies
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / microbiology
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Young Adult

Substances

  • IL17A protein, human
  • Interleukin-17
  • Interleukin-27