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Effects of Helicobacter pylori infection on gastric inflammation and local cytokine production in histamine-deficient (histidine decarboxylase knock-out) mice.

Abstract：

UNLABELLED:Helicobacter pylori infection in humans causes gastritis. The infection elicits a complex immune response in which the activation of mast cells and histamine release is of particular importance. Histamine further promotes the immune response and stimulates gastric acid secretion. The inflammatory effects of H. pylori can be studied in intragastrically infected mice. The aim of this study was to compare the local cytokine responses of histamine-deficient, histidine decarboxylase knock-out (HDC KO) and wild-type (WT) mice following H. pylori infection. METHODS:H. pylori was administered intragastrically to HDC KO and WT mice. The animals were infected three times in a 1-week-period and were sacrificed 8 weeks after the first intervention. The local TNF-alpha, IL-6 and IL-10 cytokine levels in gastric mucosal specimens were determined by ELISA. Gastric mucosa sections were also analysed for histological signs of inflammation. To investigate the antibody response following H. pylori infection, the total anti-H. pylori IgG and the ratio of IgG1/IgG2a isotypes were determined in the serum by ELISA. RESULTS:H. pylori induced considerable cytokine production in the infected groups. The TNF-alpha and IL-6 levels were significantly higher in the WT mice than in the HDC KO mice, whereas the IL-10 levels did not differ between the groups. Anti-H. pylori IgG was detected only in the infected groups and the titre was higher in the WT mice. A higher IgG1/IgG2a ratio was observed in the H. pylori infected HDC KO group. Histological analysis revealed that the grades of inflammation were less severe in the infected HDC KO animals. CONCLUSIONS:The results suggest that H. pylori induces lower TNF-alpha and IL-6 secretion in the gastric mucosa in the HDC KO mice than in the WT animals, while the levels of induction of IL-10 were similar. The imbalance between Th1/Th2 is less pronounced in the HDC KO mice, which might explain the milder inflammation in the gastric mucosa. These results provide further information on the role of histamine in the pathomechanism of H. pylori-induced gastritis.

journal_name

Immunol Lett

journal_title

Immunology letters

authors

Klausz G,Buzás E,Scharek P,Tiszlavicz L,Gyulai Z,Fülöp AK,Falus A,Mándi Y

doi

10.1016/j.imlet.2004.05.005

subject

Has Abstract

pub_date

2004-07-15 00:00:00

pages

223-8

issue

eissn

0165-2478

issn

1879-0542

pii

S0165247804001361

journal_volume

pub_type

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Effects of Helicobacter pylori infection on gastric inflammation and local cytokine production in histamine-deficient (histidine decarboxylase knock-out) mice.