Effect of cyclooxygenase-2 inhibition on human Helicobacter pylori gastritis: mechanisms underlying gastrointestinal safety and implications for cancer chemoprevention.
Cyclooxygenase (COX)-2 expression and prostaglandin production is increased by Helicobacter pylori infection. Non-selective COX inhibitors reduce prostaglandins and mucosal proliferation in infected mucosa and may reduce gastric cancer risk, but ulceration precludes their use. COX-2 inhibitors cause fewer ulcers and may be chemopreventive. Physiological studies of COX-2 inhibitors in humans with H. pylori infection have not been performed.


OBJECTIVE
To study the impact of COX-2 specific inhibition on gastric prostaglandin levels, H. pylori gastritis and proliferation.


METHODS
Twenty infected (eight males, 12 females; age 38 +/- 1.8) and six uninfected (four males, two females; age 36 +/- 3.5) healthy volunteers received rofecoxib 25 mg daily for 14 days. Endoscopic biopsies were evaluated for prostaglandin E2 (PGE2) content, gastritis and proliferation.


RESULTS
Before drug therapy, compared to uninfected, H. pylori-infected subjects had significantly higher: (a) gastric mucosal PGE2 (pg/mg tissue) in the gastric body and antrum, (b) H. pylori score in body and antrum and (c) mid-gland proliferation index in antrum and body. The COX-2 inhibitor did not significantly affect PGE2 levels, gastritis scores or proliferation indices in the body or antrum in the H. pylori-positive or -negative subjects.


CONCLUSIONS
The predominant source of increased gastric PGE2 in H. pylori infection appears to be COX-1-derived. In non-ulcerated H. pylori gastritis, COX-2 inhibition does not affect cellular proliferation. Rofecoxib's lack of effect on gastric prostaglandin levels and proliferation in H. pylori-infected mucosa may explain the absence of an increased ulcer risk among COX-2 inhibitor users with H. pylori infection. The lack of significant effect on intermediate biomarkers raises uncertainty regarding the potential of specific COX-2 inhibitors for chemoprevention of gastric cancer.
Scheiman
J M
JM
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. jscheima@umich.edu
Greenson
J K
JK
Lee
J
J
Cryer
B
B
D000328:Adult; D002455:Cell Division; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016480:Helicobacter pylori; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007783:Lactones / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011706:Pyloric Antrum / Q000378:metabolism; D013274:Stomach Neoplasms / Q000517:prevention & control*; D013450:Sulfones
D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone