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. 2001 Jun;48(6):765–773. doi: 10.1136/gut.48.6.765

Effects of Helicobacter pylori infection on gastric acid secretion and serum gastrin levels in Mongolian gerbils

M Takashima 1, T Furuta 1, H Hanai 1, H Sugimura 1, E Kaneko 1
PMCID: PMC1728329  PMID: 11358893

Abstract

BACKGROUND AND AIMS—Body gastritis caused by Helicobacter pylori infection appears to inhibit gastric acid secretion. The aim of this study was to determine the effects of H pylori infection on gastric acid secretion and clarify its mechanisms with reference to interleukin 1β (IL-1β).
METHODS—(1) Mongolian gerbils were inoculated orally with H pylori. Before, six, and 12 weeks after inoculation, serum gastrin levels, gastric acid output, and IL-1β mRNA levels in the gastric mucosa were determined. Pathological changes were also determined according to the updated Sydney system. (2) Effects of recombinant human IL-1 receptor antagonist (rhIL-1ra) on gastric acid output and serum gastrin levels were also determined.
RESULTS—(1) Scores for activity and inflammation of gastritis and serum gastrin levels were significantly increased, and gastric acid output was significantly decreased six and 12 weeks after inoculation with H pylori. IL-1β mRNA levels in the gastric mucosa were also elevated six and 12 weeks after inoculation with H pylori. (2) Acid output and serum gastrin levels in the infected groups returned to control levels after rhIL-1ra injection.
CONCLUSIONS—Gastric acid secretion is decreased and serum gastrin levels are increased in Mongolian gerbils infected with H pylori. This change in gastric acid secretion appears to be mediated by IL-1β induced by H pylori infection.


Keywords: Helicobacter pylori; interleukin 1β; Mongolian gerbils; gastric acid; gastrin

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Figure 1  .

Figure 1  

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Oligonucleotide sequences of polymerase chain reaction (PCR) primers and competitive templates. The primer pair for Mongolian gerbil interleukin 1β (IL-1β) amplifies a 296 bp band. The primer pair for β-actin amplifies a 164 bp band. The competitive template for Mongolian gerbil IL-1β is 150 bp long, and that for β-actin is 82 bp long. PCR products of cDNA are distinguished by size from those of competitors.

Figure 2  .

Figure 2  

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(A) Mongolian gerbil interleukin 1β (IL-1β) (296 bp) versus competitor (150 bp). Lane M is the size marker (øX174 digested with Hae III). Lanes 1-8 contain eightfold serial amounts of competitor DNA ranging from 1.0×10-0.5 pg/µl to 1.0×103 pg/µl competing against a fixed dose of cDNA. (B) β-actin (164 bp) versus competitor (82 bp). Lane M is the size marker (øX174 digested with Hinf I). Lanes 1-8 contain eightfold serial amounts of competitor DNA ranging from 1.0×10-0.5 pg/µl to 1.0×103 pg/µl competing against a fixed dose of cDNA.

Figure 3  .

Figure 3  

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(A) Logarithmic plot of the ratio of Mongolian gerbil interleukin 1β (IL-1β, 296 bp) to competitor (150 bp), corresponding to fig 2A. The quantity of IL-1β mRNA in the reaction tube was determined by calculating how much of the competitor was required to achieve equal amounts of product. The amount of IL-1β mRNA was then calculated by extrapolating from the intersection of the curves to the x axis where the amounts of IL-1β (296 bp) and competitor were equal. (B) Logarithmic plot of the ratio of β-actin (164 bp) to competitor (82 bp), corresponding to fig 2B.

Figure 4  .

Figure 4  

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Histopathological changes in the gastric mucosa of Mongolian gerbils. (A) Inflammatory cell infiltrations were not observed in the control groups six weeks after inoculation. (B) Marked inflammatory cell infiltrations were observed in the infected groups six weeks after inoculation with H pylori. (C) Inflammatory cell infiltrations were not observed in the control groups 12 weeks after inoculation. (D) Severe inflammatory cell infiltrations were observed in the infected groups 12 weeks after inoculation with H pylori (haematoxylin-eosin, ×100).

Figure 5  .

Figure 5  

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(A) Changes in gastritis scores for activity from before to six and 12 weeks after inoculation in the infected (Helicobacter pylori (HP+)) and control (HP−) groups. The variables used for grading gastritis were rated on a four point scale: 0, absent; 1, mild; 2, moderate; and 3, severe, in accordance with the Sydney system. Gastritis scores for activity in the infected groups significantly increased six and 12 weeks after H pylori inoculation. No significant changes were observed in the control groups. (B) Changes in gastritis scores for inflammation from before to six and 12 weeks after inoculation in the infected and control groups. Gastritis scores for inflammation in the infected groups significantly increased six and 12 weeks after H pylori inoculation. No significant changes were observed in the control groups.

Figure 6  .

Figure 6  

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Changes in gastric acid output from before to six and 12 weeks after inoculation in the infected (Helicobacter pylori (HP+)) and control (HP−) groups. Gastric acid output in the infected groups significantly decreased six and 12 weeks after H pylori inoculation. No significant changes were observed in the control groups. *p=0.0328; **p=0.0061 compared with before inoculation.

Figure 7  .

Figure 7  

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Changes in serum gastrin levels from before to 6 and 12 weeks after inoculation. Serum gastrin levels in the infected (Helicobacter pylori (HP+)) groups significantly increased six and 12 weeks after H pylori inoculation. No significant changes were observed in the control groups (HP−). *p=0.0014; **p=0.0008 compared with before innoculation.

Figure 8  .

Figure 8  

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(A) Alignment of the 296 bp portion of interleukin 1β (IL-1β) cDNA sequences for the Mongolian gerbil, human, and mouse. Oligonucleotides in bold type in human and mouse are different from those of Mongolian gerbil; 85.1% oligonucleotide identities were observed between Mongolian gerbil and human and 90.2% between Mongolian gerbil and mouse. (B) Alignment of the 164 bp portion of β-actin cDNA sequences for the three species. Oligonucleotides in bold type in human and mouse were different from those of the Mongolian gerbil; 97.0% oligonucleotide identities were observed between Mongolian gerbil and human and 96.3% between Mongolian gerbil and mouse.

Figure 9  .

Figure 9  

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Changes in interleukin 1β (IL-1β) mRNA levels from before to six and 12 weeks after inoculation in the infected (Helicobacter pylori (HP+)) and control (HP−) groups. Il-1β mRNA levels significantly increased six and 12 weeks after H pylori inoculation. IL-1β mRNA was virtually undetected in the control groups throughout the study. *p=0.0191; **p=0.0006 compared with before innoculation.

Figure 10  .

Figure 10  

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Gastric acid output with (+) or without (−) recombinant human IL-1 receptor antagonist (rhIL-1ra) injection in the infected (Helicobacter pylori (HP+)) and control (HP−) groups. Gastric acid output significantly increased to control levels after rhIL-1ra injection in the infected groups whereas no significant changes were observed after rhIL-1ra injection in the control groups.

Figure 11  .

Figure 11  

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Serum gastrin levels with (+) or without (−) recombinant human IL-1 receptor antagonist (rhIL-1ra) injection in the infected (Helicobacter pylori (HP+)) and control (HP−) groups. Serum gastrin levels significantly decreased to control levels after rhIL-1ra injection in the infected groups whereas no significant changes were observed after rhIL-1ra injection in the control groups.

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