Interaction of NSAIDs and Helicobacter pylori on gastrointestinal injury and prostaglandin production: a controlled double-blind trial.
BACKGROUND
H. pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are major causes of gastroduodenal injury in man. We assessed the effect of daily NSAID ingestion on gastric histology and the interaction of H. pylori infection and NSAID ingestion on gross and histological injury and prostaglandin production.


METHODS
Fifty-two healthy volunteers with normal baseline endoscopy were randomly assigned to receive identical-appearing naproxen 500 mg b.d., etodolac 400 mg b.d., or placebo b.d. for 4 weeks. The number and size of all erosions and ulcers were recorded by endoscopy at weeks 1 and 4. Biopsies taken at baseline, week 1 and week 4 were assessed for H. pylori, histology and gastric prostaglandin E2 production.


RESULTS
No significant changes occurred with treatment in any histological feature in the three study groups or in H. pylori positive or negative subsets. Antral inflammation scores (scale, 0-6) for the NSAID group were: week 0--1.2 +/- 0.3; week 1--1.1 +/- 0.3; week 4--1.3 +/- 0.3; findings of 'chemical gastritis' were not seen. No significant difference in gross gastroduodenal injury (number or total surface area of ulcers or erosions) was seen between H. pylori positive and negative subjects in the three groups at week 1 or 4. Baseline prostaglandin E2 production was significantly higher in H. pylori positive subjects (2398 +/- 400 vs. 1064 +/- 255 pg/mg protein) and decreased significantly with 1 week of naproxen in H. pylori positive and negative subjects.


CONCLUSIONS
NSAID ingestion does not cause diffuse histological injury. Any diffuse histological injury in the gastric mucosa is related to the presence of H. pylori, and this H. pylori-associated gastritis is not altered by NSAID ingestion. Furthermore, the development of gross gastroduodenal damage with 4 weeks of NSAID use is not influenced by underlying H. pylori infection.
Laine
L
L
Gastroenterology Division, USC, School of Medicine 90033, USA.
Cominelli
F
F
Sloane
R
R
Casini-Raggi
V
V
Marin-Sorensen
M
M
Weinstein
W M
WM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004311:Double-Blind Method; D017308:Etodolac / Q000494:pharmacology; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000209:etiology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008875:Middle Aged; D009288:Naproxen / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D013276:Stomach Ulcer / Q000188:drug therapy
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D017308:Etodolac; D009288:Naproxen