Anti-inflammatory and tissue-protectant drug effects: results from a randomized placebo-controlled trial of gastritis patients at high risk for gastric cancer.
BACKGROUND
The inflammatory process involving Helicobacter pylori-associated gastritis is thought to lead to epithelial damage and contribute to the development of gastric cancer. Evidence exists from animal and in vitro studies suggesting that tetracyclines have both anti-inflammatory and tissue-protectant effects unrelated to their antimicrobial activity. We attempted to modulate components of H. pylori's inflammatory process by: (i) eliminating the infection; (ii) using tetracycline to alter the host's reaction to the infection without reducing the bacterial load; and (iii) using calcium to counteract the effect of excessive dietary salt.


METHODS
We conducted a 16-week placebo-controlled clinical trial with 374 H. pylori-associated gastritis patients randomly assigned to one of five groups: (1) triple therapy consisting of metronidazole, amoxicillin and bismuth subsalicylate for 2 weeks, followed by bismuth alone for 14 weeks; (2) calcium carbonate; (3) triple therapy and calcium carbonate; (4) tetracycline; or (5) placebo.


RESULTS
Subjects in the tetracycline and triple therapy groups, but not the calcium carbonate only group, showed a reduction in inflammation and epithelial damage vs. those in the placebo group, independent of a change in H. pylori density and other factors. Our results also indicate that epithelial damage may be affected by mechanisms independent of H. pylori density or inflammation.


CONCLUSIONS
The results are consistent with the hypothesis that tetracycline can decrease inflammation independent of a reduction in the bacterial load. More research is needed to investigate mechanisms leading to epithelial damage which are independent of H. pylori density and inflammation.
Fischbach
L A
LA
School of Public Health at Dallas, University of Texas-Houston, Health Science Center, Dallas, TX, USA. Lori.Fischbach@UTSouthwestern.edu
Correa
P
P
Ramirez
H
H
Realpe
J L
JL
Collazos
T
T
Ruiz
B
B
Bravo
L E
LE
Bravo
J C
JC
Casabon
A L
AL
Schmidt
B A
BA
D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000627:therapeutic use*; D000863:Antacids / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001729:Bismuth / Q000627:therapeutic use*; D002119:Calcium Carbonate / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004848:Epithelium / Q000473:pathology; D005260:Female; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000302:isolation & purification* / Q000472:pathogenicity; D006801:Humans; D007249:Inflammation; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use*; D008875:Middle Aged; D009942:Organometallic Compounds / Q000627:therapeutic use*; D010406:Penicillins / Q000627:therapeutic use*; D010919:Placebos; D012307:Risk Factors; D012459:Salicylates / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000209:etiology / Q000517:prevention & control; D013752:Tetracycline / Q000494:pharmacology*; D016896:Treatment Outcome
D000863:Antacids; D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; D010406:Penicillins; D010919:Placebos; D012459:Salicylates; D008795:Metronidazole; C015715:bismuth subsalicylate; D000658:Amoxicillin; D013752:Tetracycline; D002119:Calcium Carbonate; D001729:Bismuth