title: Treatment of Helicobacter gastritis with IL-4 requires somatostatin.
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-gamma, 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.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yana
authors.initials: Y
authors.lastname: Zavros
authors.forename: Sivaprakash
authors.initials: S
authors.lastname: Rathinavelu
authors.forename: John Y
authors.initials: JY
authors.lastname: Kao
authors.forename: Andrea
authors.initials: A
authors.lastname: Todisco
authors.forename: John
authors.initials: J
authors.lastname: Del Valle
authors.forename: Joel V
authors.initials: JV
authors.lastname: Weinstock
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Low
authors.forename: Juanita L
authors.initials: JL
authors.lastname: Merchant
mesh_terms: D000818:Animals; D005744:Gastric Acid; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D044922:Helicobacter felis; D007249:Inflammation; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D013004:Somatostatin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D015847:Interleukin-4; D013004:Somatostatin; D007371:Interferon-gamma