Treatment of Helicobacter gastritis with IL-4 requires somatostatin

Yana Zavros, Sivaprakash Rathinavelu, John Y. Kao, Andrea Todisco, John Del Valle, Joel V. Weinstock, Malcolm J. Low, Juanita L. Merchant

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Fifty percent of the world's population is infected with Helicobacter pylori, however, treatment has been insufficient to eradicate the organisms due to rising antibiotic resistance. Helicobacter infection is characterized by induction of a T helper 1 lymphocyte (Th1) immune response, hypergastrinemia, and suppressed tissue somatostatin (SOM) levels, However, the mechanism by which the immune response regulates acid secretion is not known. We show here that treatment with IFN-γ, a Th1 cytokine, was sufficient to induce gastritis, increase gastrin, and decrease SOM levels within 7 days. In contrast, the T helper 2 lymphocyte cytokine IL-4 increased SOM levels and effectively suppressed gastrin expression and secretion. This result demonstrated reciprocal regulation of acid regulatory peptides by immune modulators. IL-4 pretreatment prevented gastritis in infected wild-type but not in SOM null mice. Thus, the ability of IL-4 to oppose a Th1-mediated infection required SOM. Immunofluorescence was used to document the presence of IL-4 receptors on the gastric SOM-secreting cell (D cell). Moreover, IL-4 stimulated SOM release from primary D cell cultures. Treatment of mice chronically infected with Helicobacter felis for 2 mo with the SOM analogue octreotide resolved the inflammation. Thus, a mechanism by which IL-4 resolves inflammation in the stomach is by stimulating the release of SOM from gastric D cells.

Original languageEnglish (US)
Pages (from-to)12944-12949
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number22
DOIs
StatePublished - Oct 28 2003
Externally publishedYes

Keywords

  • Gastrin
  • IFN-γ
  • Inflammation
  • Octreotide
  • Th2

ASJC Scopus subject areas

  • General

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