Teprenone, but not H2-receptor blocker or sucralfate, suppresses corpus Helicobacter pylori colonization and gastritis in humans: teprenone inhibition of H. pylori-induced interleukin-8 in MKN28 gastric epithelial cell lines.
BACKGROUND
The role of teprenone in Helicobacter pylori-associated gastritis has yet to be determined. To investigate the effect of teprenone on inflammatory cell infiltration, and on H. pylori colonization of the gastric mucosa in H. pylori-infected patients, we first compared the effect of teprenone with that of both histamine H2 receptor antagonists (H2-RA) and sucralfate on the histological scores of H. pylori gastritis. We then examined its in vitro effect on H. pylori-induced interleukin (IL)-8 production in MKN28 gastric epithelial cells.


METHODS
A total of 68 patients were divided into three groups, each group undergoing a 3-month treatment with either teprenone (150 mg/day), H2-RA (nizatidine, 300 mg/day), or sucralfate (3 g/day). All subjects underwent endoscopic examination of the stomach before and after treatment. IL-8 production in MKN28 gastric epithelial cells was measured by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Following treatment, the teprenone group showed a significant decrease in both neutrophil infiltration and H. pylori density of the corpus (before vs. after: 2.49 +/- 0.22 vs. 2.15 +/- 0.23, p =.009; 2.36 +/- 0.25 vs. 2.00 +/- 0.24, p =.035, respectively), with no significant differences seen in either the sucralfate or H2-RA groups. Teprenone inhibited H. pylori-enhanced IL-8 production in MKN28 gastric epithelial cells in vitro, in a dose-dependent manner.


CONCLUSIONS
Teprenone may modify corpus H. pylori-associated gastritis through its effect on neutrophil infiltration and H. pylori density, in part by its inhibition of IL-8 production in the gastric mucosa.
Miyake
Kazumasa
K
Third Department of Internal Medicine, Department of Pathology, Tokyo, Japan.
Tsukui
Taku
T
Shinji
Yoko
Y
Shinoki
Kei
K
Hiratsuka
Tetsuro
T
Nishigaki
Hitoshi
H
Futagami
Seiji
S
Wada
Ken
K
Gudis
Katya
K
Iwakiri
Katsuhiko
K
Yamada
Nobutaka
N
Sakamoto
Choitsu
C
D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use; D001706:Biopsy; D002460:Cell Line; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000188:drug therapy* / Q000276:immunology; D016481:Helicobacter Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000254:growth & development; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration; D016567:Nizatidine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020116:Pepsinogen A / Q000032:analysis; D020115:Pepsinogen C / Q000032:analysis; D013392:Sucralfate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014510:Urease / Q000032:analysis
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D006635:Histamine H2 Antagonists; D016209:Interleukin-8; D013392:Sucralfate; D020115:Pepsinogen C; D020116:Pepsinogen A; D014510:Urease; D016567:Nizatidine; C031049:geranylgeranylacetone