Document Detail


Treatment of Helicobacter gastritis with IL-4 requires somatostatin.
MedLine Citation:
PMID:  14555768     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Yana Zavros; Sivaprakash Rathinavelu; John Y Kao; Andrea Todisco; John Del Valle; Joel V Weinstock; Malcolm J Low; Juanita L Merchant
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2003-10-10
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  100     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-29     Completed Date:  2004-01-05     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12944-9     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Gastric Acid
Gastric Mucosa / pathology,  secretion
Gastritis / drug therapy,  immunology,  microbiology*,  pathology
Helicobacter Infections / drug therapy*,  immunology,  pathology
Helicobacter felis*
Inflammation
Interferon-gamma / genetics
Interleukin-4 / therapeutic use*
Mice
Mice, Inbred C57BL
Mice, Knockout
Polymerase Chain Reaction
Somatostatin / deficiency,  genetics,  physiology*,  secretion
Grant Support
ID/Acronym/Agency:
CA 46952/CA/NCI NIH HHS; DK 34533/DK/NIDDK NIH HHS; DK 41301/DK/NIDDK NIH HHS; DK 45729/DK/NIDDK NIH HHS; DK 61410/DK/NIDDK NIH HHS; DL 62041//PHS HHS
Chemical
Reg. No./Substance:
207137-56-2/Interleukin-4; 51110-01-1/Somatostatin; 82115-62-6/Interferon-gamma
Comments/Corrections

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